CINXE.COM
Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment - PubMed
<!DOCTYPE html> <html lang="en" > <head itemscope itemtype="http://schema.org/WebPage" prefix="og: http://ogp.me/ns#" > <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <!-- Mobile properties --> <meta name="HandheldFriendly" content="True"> <meta name="MobileOptimized" content="320"> <meta name="viewport" content="width=device-width, initial-scale=1.0"> <link rel="preconnect" href="https://cdn.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.ncbi.nlm.nih.gov"> <link rel="preconnect" href="https://www.google-analytics.com"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.5ecf62baa0fa.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.452c70ce66f7.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.7bf600913d6e.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.0bfa59184c7a.css" type="text/css"> <link rel="stylesheet" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/css/output.b576742ffc3e.css" type="text/css"> <title>Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment - PubMed</title> <link rel="preload" as="font" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/uswds/dist/fonts/merriweather-bold-webfont.woff2" type="font/woff2" crossorigin /> <!-- Favicons --> <link rel="shortcut icon" type="image/ico" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon.ico" /> <link rel="icon" type="image/png" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon.png" /> <!-- 192x192, as recommended for Android http://updates.html5rocks.com/2014/11/Support-for-theme-color-in-Chrome-39-for-Android --> <link rel="icon" type="image/png" sizes="192x192" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-192.png" /> <!-- 57x57 (precomposed) for iPhone 3GS, pre-2011 iPod Touch and older Android devices --> <link rel="apple-touch-icon-precomposed" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-57.png"> <!-- 72x72 (precomposed) for 1st generation iPad, iPad 2 and iPad mini --> <link rel="apple-touch-icon-precomposed" sizes="72x72" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-72.png"> <!-- 114x114 (precomposed) for iPhone 4, 4S, 5 and post-2011 iPod Touch --> <link rel="apple-touch-icon-precomposed" sizes="114x114" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-114.png"> <!-- 144x144 (precomposed) for iPad 3rd and 4th generation --> <link rel="apple-touch-icon-precomposed" sizes="144x144" href="https://cdn.ncbi.nlm.nih.gov/coreutils/nwds/img/favicons/favicon-144.png"> <!-- For Pinger + Google Optimize integration (NS-820) --> <meta name="ncbi_sg_optimize_id" content=""> <!-- Mobile browser address bar color --> <meta name="theme-color" content="#20558a"> <!-- Preserve the Referrer when going from HTTPS to HTTP --> <meta name="referrer" content="origin-when-cross-origin"> <meta name="ncbi_pinger_gtm_track" content="true"/> <!-- Logging params: Pinger defaults --> <meta name="ncbi_app" content="pubmed" /> <meta name="ncbi_db" content="pubmed" /> <meta name="ncbi_phid" content="F89F0001B8D2F72500002EA210DEED55.1.m_6" /> <meta name="ncbi_pinger_stat_url" content="https://www.ncbi.nlm.nih.gov/stat" /> <meta name="log_category" content="literature" /> <meta name="ncbi_cost_center" content="pubmed" /> <!-- Logging params: Pinger custom --> <meta name="ncbi_pdid" content="abstract" /> <meta name="log_op" content="retrieve" /> <meta name="uid" content="36932102" /> <meta name="ncbi_uid" content="36932102" /> <meta name="log_displayeduids" content="36932102" /> <meta name="log_source_db" content="pubmed,pmc" /> <meta name="log_icons_present" content="true" /> <!-- Social meta tags for unfurling urls --> <meta name="description" content="Enzyme-catalyzed replication of nucleic acid sequences is a prerequisite for the survival and evolution of biological entities. Before the advent of protein synthesis, genetic information was most likely stored in and replicated by RNA. However, experimental systems for sustained RNA-dependent RNA-r …"><meta name="keywords" content="pmid:36932102, PMC10023712, doi:10.1038/s41467-023-37206-4, Research Support, Non-U.S. Gov't, Annalena Salditt, Leonie Karr, Hannes Mutschler, Base Sequence, Nucleic Acid Conformation, RNA / genetics, RNA / metabolism, RNA, Antisense / genetics, RNA, Catalytic* / genetics, RNA, Catalytic* / metabolism, RNA-Dependent RNA Polymerase / metabolism, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/36932102/"><meta property="og:description" content="Enzyme-catalyzed replication of nucleic acid sequences is a prerequisite for the survival and evolution of biological entities. Before the advent of protein synthesis, genetic information was most likely stored in and replicated by RNA. However, experimental systems for sustained RNA-dependent RNA-r …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/36932102/"><meta name="twitter:description" content="Enzyme-catalyzed replication of nucleic acid sequences is a prerequisite for the survival and evolution of biological entities. Before the advent of protein synthesis, genetic information was most likely stored in and replicated by RNA. However, experimental systems for sustained RNA-dependent RNA-r …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"> <!-- OpenSearch XML --> <link rel="search" type="application/opensearchdescription+xml" href="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/opensearch.xml" title="PubMed search"> <!-- Disables severely broken elements when no JS --> <noscript> <link rel="stylesheet" type="text/css" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/no-script.css"> </noscript> <meta name="citation_title" content="Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment"> <meta name="citation_authors" content="Salditt A;Karr L;Salibi E;Le Vay K;Braun D;Mutschler H;"> <meta name="citation_date" content="03/17/2023"> <meta name="citation_publisher" content="Nat Commun"> <meta name="citation_journal_title" content="Nature communications"> <meta name="citation_pmid" content="36932102"> <meta name="citation_abstract_html_url" content="https://pubmed.ncbi.nlm.nih.gov/36932102/"> <meta name="citation_volume" content="14"> <meta name="citation_issue" content="1"> <meta name="citation_doi" content="10.1038/s41467-023-37206-4"> <meta name="citation_issn" content="2041-1723"> <link rel="canonical" href="https://pubmed.ncbi.nlm.nih.gov/36932102/" /> </head> <body > <noscript> <div class="no-script-banner" id="no-script-banner"> <div class="warning-message"> <div class="warning-message-text"> This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! </div> </div> </div> </noscript> <div class="no-session-banner" id="no-session-banner" hidden> <div class="warning-message"> <div class="warning-message-text"> Clipboard, Search History, and several other advanced features are temporarily unavailable. </div> <button class="close-banner-button" title="Close Clipboard and Search History not available warning banner" ref="linksrc=close_no_session_banner" aria-controls="no-session-banner" aria-label="Close Clipboard and Search History not available warning banner" aria-expanded="true"> </button> </div> </div> <a class="usa-skipnav" href="#article-details"> Skip to main page content </a> <!-- ========== BEGIN HEADER ========== --> <section class="usa-banner"> <div class="usa-accordion"> <header class="usa-banner-header"> <div class="usa-grid usa-banner-inner"> <img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" /> <p>An official website of the United States government</p> <button class="usa-accordion-button usa-banner-button" aria-expanded="false" aria-controls="gov-banner-top" > <span class="usa-banner-button-text">Here's how you know</span> </button> </div> </header> <div class="usa-banner-content usa-grid usa-accordion-content" id="gov-banner-top" > <div class="usa-banner-guidance-gov usa-width-one-half"> <img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg" alt="Dot gov" /> <div class="usa-media_block-body"> <p> <strong>The .gov means it’s official.</strong> <br /> Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site. </p> </div> </div> <div class="usa-banner-guidance-ssl usa-width-one-half"> <img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg" alt="Https" /> <div class="usa-media_block-body"> <p> <strong>The site is secure.</strong> <br /> The <strong>https://</strong> ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. </p> </div> </div> </div> </div> </section> <div class="usa-overlay"></div> <header class="ncbi-header" role="banner" data-section="Header"> <div class="usa-grid"> <div class="usa-width-one-whole"> <div class="ncbi-header__logo"> <a href="https://www.ncbi.nlm.nih.gov/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo"> <img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" /> </a> </div> <div class="ncbi-header__account"> <a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a> <button id="account_info" class="header-button" style="display:none" aria-controls="account_popup"> <span class="fa fa-user" aria-hidden="true"></span> <span class="username desktop-only" aria-hidden="true" id="uname_short"></span> <span class="sr-only">Show account info</span> </button> </div> <div class="ncbi-popup-anchor"> <div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true"> <div class="ncbi-popup-head"> <button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu"><span class="fa fa-times"></span><span class="usa-sr-only">Close</span></button> <h4>Account</h4> </div> <div class="account-user-info"> Logged in as:<br/> <b><span class="username" id="uname_long">username</span></b> </div> <div class="account-links"> <ul class="usa-unstyled-list"> <li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li> <li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li> <li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li> <li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li> </ul> </div> </div> </div> </div> </div> </header> <div role="navigation" aria-label="access keys"> <a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a> <a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a> <a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a> <a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a> <a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a> </div> <section data-section="Alerts"> <div class="ncbi-alerts-placeholder"></div> </section> <!-- ========== END HEADER ========== --> <a id="maincontent" aria-label="Main page content below" role="navigation"></a> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <form action="/" method="get" autocomplete="off" class="usa-search usa-search-big search-form content-page-layout" id="search-form" role="search"> <div class="inner-wrap"> <a class="pubmed-logo" aria-label="Pubmed Logo" href="/" data-ga-category="featured_link" data-ga-action="pubmed_logo"> <img src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/images/pubmed-logo-blue.svg" alt="pubmed logo" /> </a> <a href="#" class="search-input-trigger" data-alt-title="Hide search bar" title="Show search bar" aria-label="Show search bar"> </a> <div role="search" class="search-input"> <div class="form-field "> <label class="usa-sr-only" for="id_term"> Search: </label> <input type="search" name="term" data-skip-ie-scroll-to-top="" data-replace-term-with-exact="" data-exact-query="" placeholder="" class="term-input" required="required" id="id_term"/><a href="#" class="clear-btn" aria-label="Clear search input" title="Clear search input" role="button" data-pinger-ignore></a><button type="submit" class="search-btn" aria-label="Search" disabled data-pinger-ignore><span class="usa-search-submit-text">Search</span></button> </div> </div> <!-- Create alert and Create RSS are buttons that look like links --> <!-- Better for them to look like buttons but no space --> <div class="search-links-wrapper content-page-layout"> <div class="search-links"> <a href="/advanced/" class="search-input-link adv-search-link" data-ga-category="featured_link" data-ga-action="adv_search">Advanced</a> <a href="/clipboard/" class="search-input-link clipboard-link hidden" data-ga-category="featured_link" data-ga-action="clipboard"> Clipboard <span class="amount-in-clipboard"></span> </a> </div> <span class="search-input-link user-guide-link" role="navigation" aria-label="User guide"> <a href="/help/" data-ga-category="featured_link" data-ga-action="user_guide"> User Guide </a> </span> </div> </div> </form> <div id="article-page-header"> <div id="article-top-actions-bar" class="article-top-actions-bar"> <div class="inner-wrap"> <div class="actions-container"> <div class="return-to-search"> </div> <div class="multiple-results-actions " role="region" aria-label="save, email, send to"> <button id="save-results-panel-trigger" type="button" class="save-results save-results-panel-trigger" aria-expanded="false" aria-controls="save-action-panel" data-ga-category="save_share" data-ga-action="save" data-ga-label="open"> Save </button><button id="email-results-panel-trigger" type="button" class="email-results email-results-panel-trigger" aria-expanded="false" aria-controls="email-action-panel" data-ga-category="save_share" data-ga-action="email" data-ga-label="open"> Email </button><div class="more-actions dropdown-block"><button id="more-actions-trigger" type="button" class="trigger more-actions-trigger" ref="linksrc=show_moreactions_btn" aria-label="Send to" aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link " href="#" role="button" data-ga-category="save_share" data-ga-action="clipboard" data-ga-label="send"> Clipboard </a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36932102%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36932102%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div> </div> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span class="button-label">Display options</span> </button> <div class="dropdown" hidden> <div class="title"> Display options </div> <div class="content"> <div class="format-container"> <span class="option-label"> Format </span> <select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format"> <option value="abstract">Abstract</option> <option value="pubmed">PubMed</option> <option value="pmid">PMID</option> </select> </div> </div> </div> </div> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> </div> </div> </div> <div id="article-panels-container" class="article-panels-container"> <div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Save citation to file </h2> <form id="save-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <div class="action-panel-control-wrap"> <label for="save-action-format" class="action-panel-label"> Format: </label> <select id="save-action-format" name="results-format" class="action-panel-selector"> <option value="summary-text">Summary (text)</option> <option value="pubmed-text">PubMed</option> <option value="pmid">PMID</option> <option value="abstract">Abstract (text)</option> <option value="csv">CSV</option> </select> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="save" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Save citations to file' panel" ref="linksrc=close_save_panel" aria-controls="save-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="save" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="email-action-panel" class="email-action-panel action-panel" aria-hidden="true" data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback" data-recaptcha-enabled="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Email citation </h2> <form id="email-action-panel-form" class="action-panel-content action-form" action="/send-email/" data-by-search-action="/results-export-email-by-search-data/" data-by-ids-action="/send-email/" data-by-search-method="post" data-by-ids-method="post" method="post" > <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <div class="action-panel-control-wrap"> <span class="action-panel-label"> Subject: </span> <span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 36932102 - PubMed</span> <input type="hidden" name="email-subject" value="1 selected item: 36932102"/> <input type="hidden" name="email-subject-hash" value="608d140258b27b3babc57dd1781cae922466bf7383856bb7845a9922da198eca"/> </div> <div class="action-panel-control-wrap"> <label for="email-to" class="action-panel-label required-field-asterisk"> To: </label> <input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required> </div> <div class="action-panel-control-wrap"> <label for="email-from" class="action-panel-label"> From: </label> <input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256"> </div> <div class="action-panel-control-wrap"> <label for="email-citation-format" class="action-panel-label"> Format: </label> <select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format"> <option selected="selected" value="summary">Summary</option> <option value="summary-text">Summary (text)</option> <option value="abstract">Abstract</option> <option value="abstract-text">Abstract (text)</option> </select> </div> <div class="include-supplemental-container"> <input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental"> <label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label> </div> <div class="form-field recaptcha "> <div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div> </div> <div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="email" data-ga-label="send"> Send email </button> <button class="action-panel-cancel" aria-label="Close 'Email citations' panel" ref="linksrc=close_email_panel" aria-controls="email-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="email" data-ga-label="cancel"> Cancel </button> </div> <input type="hidden" name="email-search-details" value="" /> <input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" /> </form> </div> </div> <div id="collections-action-panel" class="collections-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-collections-open-panel-enabled="false" data-collections-open-panel-url-hash="#open-collections-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to Collections </h3> <form id="collections-action-panel-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-myncbi-max-collection-name-length="100" data-add-to-collection-max-amount="1000" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <div class="choice-group" role="radiogroup"> <ul class="radio-group-items"> <li> <input type="radio" id="collections-action-panel-new" class="collections-new" name="collections" value="new" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_new"> <label for="collections-action-panel-new">Create a new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="36932102"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://doi.org/10.1038/s41467-023-37206-4" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3094&itool=Abstract-def&log$=linkouticon&uid=36932102&db=pubmed&nlmid=101528555" title="See full text options at Nature Publishing Group" data-ga-category="full_text" data-ga-action="Nature Publishing Group" data-ga-label="36932102" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.nature.com-static-images-logos-nature-portfolio-120.png" alt="full text provider logo"><span class="text"> Nature Publishing Group </span></a><a class="link-item pmc " href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/36932102/" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=36932102&db=pubmed&nlmid=101528555" title="Free full text at PubMed Central" data-ga-category="full_text" data-ga-action="PMC" data-ga-label="36932102" ><span class="text"> Free PMC article </span></a> </div> </div> <div class="short-view"> <a href="#" class="full-text-links-button full-text-links-dialog-trigger"> Full text links </a> </div> </div> <div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/36932102/citations/" data-citation-style="nlm" data-pubmed-format-link="/36932102/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="36932102" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger" aria-label="Save article in MyNCBI collections." data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_button" data-collections-open-dialog-enabled="false" data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36932102%2F%23open-collections-dialog" data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog" class="dialog collections-dialog" aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-myncbi-max-collection-name-length="100" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="sidebar-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="social-sharing"> <h3 class="title"> Share </h3> <ul class="social-sharing-links usa-unstyled-list"> <li> <a href="http://twitter.com/intent/tweet?text=Ribozyme-mediated%20RNA%20synthesis%20and%20replication%20in%20a%20model%20Hadean%20microenvironment%20https%3A//pubmed.ncbi.nlm.nih.gov/36932102/" class="share-link share-link-twitter" rel="noreferrer noopener" target="Pubmed-Social-Media-Share-Popup" title="Share article on Twitter" data-ga-category="save_share" data-ga-action="social" data-ga-label="twitter"></a> </li> <li> <a href="http://www.facebook.com/sharer/sharer.php?u=https%3A//pubmed.ncbi.nlm.nih.gov/36932102/" class="share-link share-link-facebook" rel="noreferrer noopener" target="Pubmed-Social-Media-Share-Popup" title="Share article on Facebook" data-ga-category="save_share" data-ga-action="social" data-ga-label="fb"></a> </li> <li> <div class="share-permalink"> <button class="trigger" title="Show article permalink" ref="linksrc=show_permalink_btn"> </button> <div class="dropdown" hidden> <div class="title"> Permalink </div> <div class="content"> <input type="text" class="permalink-text" value="https://pubmed.ncbi.nlm.nih.gov/36932102/" aria-label="Article permalink"/><button class="permalink-copy-button usa-button-primary" title="Copy article permalink" data-ga-category="save_share" data-ga-action="link" data-ga-label="copy_link"><span class="button-title">Copy</span></button> </div> </div> </div> </li> </ul> </div> <nav class="page-navigator" role="navigation" aria-label="Page navigation"> <div class="full-view"> <h3 class="title"> Page navigation </h3> <ul class="items-list"> <li class="heading "> <a href="#heading" aria-label="navigate to Title & authors section" data-ga-category="page_nav" data-ga-action="heading"> Title & authors </a> </li> <li class="abstract "> <a href="#abstract" aria-label="navigate to Abstract section" data-ga-category="page_nav" data-ga-action="abstract"> Abstract </a> </li> <li class="conflict-of-interest "> <a href="#conflict-of-interest" aria-label="navigate to Conflict of interest statement section" data-ga-category="page_nav" data-ga-action="conflict-of-interest"> Conflict of interest statement </a> </li> <li class="figures "> <a href="#figures" aria-label="navigate to Figures section" data-ga-category="page_nav" data-ga-action="figures"> Figures </a> </li> <li class="similar "> <a href="#similar" aria-label="navigate to Similar articles section" data-ga-category="page_nav" data-ga-action="similar"> Similar articles </a> </li> <li class="citedby "> <a href="#citedby" aria-label="navigate to Cited by section" data-ga-category="page_nav" data-ga-action="citedby"> Cited by </a> </li> <li class="references "> <a href="#references" aria-label="navigate to References section" data-ga-category="page_nav" data-ga-action="references"> References </a> </li> <li class="publication-types "> <a href="#publication-types" aria-label="navigate to Publication types section" data-ga-category="page_nav" data-ga-action="publication-types"> Publication types </a> </li> <li class="mesh-terms "> <a href="#mesh-terms" aria-label="navigate to MeSH terms section" data-ga-category="page_nav" data-ga-action="mesh-terms"> MeSH terms </a> </li> <li class="substances "> <a href="#substances" aria-label="navigate to Substances section" data-ga-category="page_nav" data-ga-action="substances"> Substances </a> </li> <li class="related-links "> <a href="#related-links" aria-label="navigate to Related information section" data-ga-category="page_nav" data-ga-action="related-links"> Related information </a> </li> <li class="linkout "> <a href="#linkout" aria-label="navigate to LinkOut - more resources section" data-ga-category="page_nav" data-ga-action="linkout"> LinkOut - more resources </a> </li> </ul> </div> <select class="short-view" autocomplete="off" title="navigate to selected section" aria-label="Navigate to page section"> <option value="heading">Title & authors</option> <option value="abstract">Abstract</option> <option value="conflict-of-interest">Conflict of interest statement</option> <option value="figures">Figures</option> <option value="similar">Similar articles</option> <option value="citedby">Cited by</option> <option value="references">References</option> <option value="publication-types">Publication types</option> <option value="mesh-terms">MeSH terms</option> <option value="substances">Substances</option> <option value="related-links">Related information</option> <option value="linkout">LinkOut - more resources</option> </select> </nav> </div> </aside> <main class="article-details" id="article-details"> <!-- "Filters applied" shows only when page is redirected from search --> <!-- because search found one result --> <header class="heading" id="heading"> <div class="full-view" id="full-view-heading"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="full-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Nature communications" tabindex="0" aria-controls="full-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Nature communications" data-pinger-ignore> Nat Commun </button><div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Nature communications"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Nat+Commun%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Nat+Commun%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Nat Commun" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Nat Commun"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Nat+Commun%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Nat Commun"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Nat Commun"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Nat Commun"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2023 Mar 17;14(1):1495.</span> </div> <span class="citation-doi"> doi: 10.1038/s41467-023-37206-4. </span> </div> <h1 class="heading-title"> Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment </h1> <div class="inline-authors"> <div class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Salditt+A&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Annalena Salditt">Annalena Salditt</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Karr+L&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Leonie Karr">Leonie Karr</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Salibi+E&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Elia Salibi">Elia Salibi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Le+Vay+K&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Kristian Le Vay">Kristian Le Vay</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Braun+D&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dieter Braun">Dieter Braun</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany. dieter.braun@lmu.de." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Mutschler+H&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Hannes Mutschler">Hannes Mutschler</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany. hannes.mutschler@tu-dortmund.de." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/36932102/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="full-view-affiliation-1" id="full-view-affiliation-1" ><sup class="key">1</sup> Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany.</li> <li data-affiliation-id="full-view-affiliation-2" id="full-view-affiliation-2" ><sup class="key">2</sup> Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany.</li> <li data-affiliation-id="full-view-affiliation-3" id="full-view-affiliation-3" ><sup class="key">3</sup> Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany. dieter.braun@lmu.de.</li> <li data-affiliation-id="full-view-affiliation-4" id="full-view-affiliation-4" ><sup class="key">4</sup> Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany. hannes.mutschler@tu-dortmund.de.</li> </ul> </div> </div> </div> <ul class="identifiers" id="full-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">36932102</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC10023712&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10023712/" data-ga-category="full_text" data-ga-action="PMCID" > PMC10023712 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1038/s41467-023-37206-4&id_type=DOI" href="https://doi.org/10.1038/s41467-023-37206-4" data-ga-category="full_text" data-ga-action="DOI" > 10.1038/s41467-023-37206-4 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> <div class="short-view" id="short-view-heading"> <h1 class="heading-title"> Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Annalena Salditt</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> Nat Commun<span class="citation-separator">.</span> </span> <span class="date"> <time class="citation-year" datetime="2023">2023</time><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/36932102/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"> <span class="button-label">Display options</span> </button> <div class="dropdown" hidden> <div class="title"> Display options </div> <div class="content"> <div class="format-container"> <span class="option-label"> Format </span> <select name="format" data-initial-value="abstract" aria-label="Display format" id="mobile-display-format"> <option value="abstract">Abstract</option> <option value="pubmed">PubMed</option> <option value="pmid">PMID</option> </select> </div> </div> </div> </div> </div> <div class="extended-article-details" id="full-article-details" aria-hidden="true"> <div class="article-citation"> <div class="article-source"> <div class="journal-actions dropdown-block"><button id="short-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Nature communications" tabindex="0" aria-controls="short-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Nature communications" data-pinger-ignore> Nat Commun </button><div id="short-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Nature communications"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Nat+Commun%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Nat+Commun%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Nat Commun" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Nat Commun"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link dropdown-block-link" ref ="linksrc=search_in_nlm_catalog_link" href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Nat+Commun%22%5BTitle+Abbreviation%5D" data-ga-category="search_catalog" data-ga-action="journal_link" data-ga-label="Nat Commun"> Search in NLM Catalog </a></li><li><a class="add-to-search-link dropdown-block-link" ref ="linksrc=add_to_search_link" role="button" data-search-term='"Nat Commun"[jour]' data-ga-category="search" data-ga-action="add_to_search" data-ga-label='"Nat Commun"[jour]' href="#"> Add to Search </a></li></ul></div></div></div><span class="period">. </span><span class="cit">2023 Mar 17;14(1):1495.</span> </div> <span class="citation-doi"> doi: 10.1038/s41467-023-37206-4. </span> </div> <div class="expanded-authors" id="short-view-expanded-authors"> <div class="authors"> <h3 class="title"> Authors </h3> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Salditt+A&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Annalena Salditt">Annalena Salditt</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Karr+L&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Leonie Karr">Leonie Karr</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Salibi+E&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Elia Salibi">Elia Salibi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Le+Vay+K&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Kristian Le Vay">Kristian Le Vay</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Braun+D&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dieter Braun">Dieter Braun</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany. dieter.braun@lmu.de." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Mutschler+H&cauthor_id=36932102" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Hannes Mutschler">Hannes Mutschler</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany. hannes.mutschler@tu-dortmund.de." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Systems Biophysics and Center for NanoScience (CeNS), Ludwig Maximilian University Munich, Geschwister-Scholl-Platz 1, 80539, Munich, Germany. dieter.braun@lmu.de.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany. hannes.mutschler@tu-dortmund.de.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">36932102</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC10023712&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10023712/" data-ga-category="full_text" data-ga-action="PMCID" > PMC10023712 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1038/s41467-023-37206-4&id_type=DOI" href="https://doi.org/10.1038/s41467-023-37206-4" data-ga-category="full_text" data-ga-action="DOI" > 10.1038/s41467-023-37206-4 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/36932102/citations/" data-citation-style="nlm" data-pubmed-format-link="/36932102/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Enzyme-catalyzed replication of nucleic acid sequences is a prerequisite for the survival and evolution of biological entities. Before the advent of protein synthesis, genetic information was most likely stored in and replicated by RNA. However, experimental systems for sustained RNA-dependent RNA-replication are difficult to realise, in part due to the high thermodynamic stability of duplex products and the low chemical stability of catalytic RNAs. Using a derivative of a group I intron as a model for an RNA replicase, we show that heated air-water interfaces that are exposed to a plausible CO<sub>2</sub>-rich atmosphere enable sense and antisense RNA replication as well as template-dependent synthesis and catalysis of a functional ribozyme in a one-pot reaction. Both reactions are driven by autonomous oscillations in salt concentrations and pH, resulting from precipitation of acidified dew droplets, which transiently destabilise RNA duplexes. Our results suggest that an abundant Hadean microenvironment may have promoted both replication and synthesis of functional RNAs. </p> </div> </div> <p class="copyright" id="copyright"> © 2023. The Author(s). </p> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="conflict-of-interest" id="conflict-of-interest"> <h2 class="title"> Conflict of interest statement </h2> <div class="statement"> <p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare no competing interests.</p> </div> </div> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="fig-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970d/10023712/f3f67e15f2e0/41467_2023_37206_Fig1_HTML.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="667" data-image-height="694" data-image-alt="Fig. 1" data-pmc-id="PMC10023712" data-figure-id="Fig1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970d/10023712/8ef275a4da8e/41467_2023_37206_Fig1_HTML.gif" alt="Fig. 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="667"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="694"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 1. Heated AWI-systems create micro water… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 1. Heated AWI-systems create micro water cycles that enable RNA folding, ligation, and strand… </p> </strong> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 1. Heated AWI-systems create micro water cycles that enable RNA folding, ligation, and strand separation at low magnesium concentrations. </strong> <div class="figure-caption-contents"><b>a</b> Asymmetric heating triggers a temperature gradient across AWI compartments. This setup mimics a gas bubble inside a porous volcanic rock. RNA and ions are concentrated at the warm side of the interface by the evaporation of water. The evaporated water condenses as dew droplets on the cold side of the chamber. The droplets grow through surface tension and form a connection to the warm surface of the chamber, creating a miniature water cycle with strong fluctuations in salt concentration and pH similar to what has been described previously<sup>,</sup>. <b>b</b> The <i>sunY</i> ribozyme catalyzes templated ligation of RNA strands using guanosine nucleosides (G) as leaving group as schematically shown for the ligation substrates M1-Cy5 (red label), M2 and M3. The mechanism of ligation is based on the exon ligation step during RNA splicing by group I intron: after formation of the ribozyme substrate complex, the ligation junction of the substrate duplex is positioned in the catalytic center of the ribozyme by binding of the terminal guanine nucleotide of the downstream exon in the G-binding pocket. The aligned 3’-OH group of the upstream exon performs an inline attack on the phosphodiester bond of the bound 5’-guanosine, leading to ligation of the adjacent upstream and downstream exons and release of the guanosine and the catalytic intron. <b>c</b> PAGE analysis (two channels: SYBR Gold, blue, and Cy5, red) shows that the AWI environment enables ligation of an RNA product M123 from three RNA substrates (M1-3) at MgCl<sub>2</sub> concentrations as low as 1 mM. To produce yields similar to 5 mM MgCl<sub>2</sub> in the AWI-system, a MgCl<sub>2</sub> concentration of 50 mM is required under isothermal conditions. Source data are provided as a Source Data file.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="fig-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970d/10023712/8f990e96d4dc/41467_2023_37206_Fig2_HTML.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="675" data-image-height="1010" data-image-alt="Fig. 2" data-pmc-id="PMC10023712" data-figure-id="Fig2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970d/10023712/621a59fd911f/41467_2023_37206_Fig2_HTML.gif" alt="Fig. 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="675"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1010"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 2. Complete replication cycles of sunY… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 2. Complete replication cycles of sunY fragments. </p> </strong> <div class="figure-caption-contents"><b> a </b> Illustration (left) and PAGE analysis (right)…</div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 2. Complete replication cycles of sunY fragments. </strong> <div class="figure-caption-contents"><b>a</b> Illustration (left) and PAGE analysis (right) of separately performed template-dependent ligations of the three <i>sunY</i> fragments A123, B123, and C123. Lanes show reactions before (T<sub>0</sub>) and after 2 h of incubation. <b>b</b>–<b>c</b> Full replication cycle of fragment C123. Replication proceeds vial ligation of the RNA substrates for the sense strand (C1, C2, C3-Cy5, red) and the antisense strand (tC1-FAM, tC2, tC3, blue). In the AWI-systems, both the sense and antisense strands emerged <b>b</b> with the template present and <b>c</b> without the template present, suggesting that <i>sunY</i> partially acted as a template for antisense strand synthesis (gray box). Under isothermal conditions no products were observed after PAGE analysis. Source data are provided as a Source Data file.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="fig-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970d/10023712/a199be6535f6/41467_2023_37206_Fig3_HTML.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="672" data-image-height="607" data-image-alt="Fig. 3" data-pmc-id="PMC10023712" data-figure-id="Fig3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/970d/10023712/51972d81c89a/41467_2023_37206_Fig3_HTML.gif" alt="Fig. 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="672"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="607"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Fig. 3. Templated synthesis and release of… </p> </strong> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Fig. 3. Templated synthesis and release of active hammerhead ribozyme. </p> </strong> <div class="figure-caption-contents"><b> a </b> <i> sunY </i> catalyzes template-dependent ligation…</div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Fig. 3. Templated synthesis and release of active hammerhead ribozyme. </strong> <div class="figure-caption-contents"><b>a</b> <i>sunY</i> catalyzes template-dependent ligation of the hammerhead ribozyme (HH-min, red) from the three RNA substrates (HH1-3, red). Local variations in pH and salt concentration cause strand separation, releasing ligated HH-min, which can then bind to and cleave its substrate (blue). <b>b</b> Ligated HH-min (red, Cy5) was observed in both the non-equilibrium and isothermal environments after 2 h of incubation. Formation of cleaved hammerhead substrate (HH-sub, blue, FAM) was observed only after incubation under non-equilibrium (AWI) conditions. Control experiments without <i>sunY</i> ribozyme exhibited no HH-min assembly or HH-sub cleavage, demonstrating that the combined unligated HH-min fragments HH1-3 have no residual RNA-cleavage activity. The isothermal control also showed no activity. Individual gel lanes (outlined with dotted lines) have been rearranged for clarity. <b>c</b> Bar graph showing the calculated yields of HH-sub cleavage after 2 h and 4 h in the AWI-system and under isothermal control conditions. Data are presented as mean values ± SEM. Black circles represent the values from independent replicates with <i>n</i> = 10 for 2 h incubation and <i>n</i> = 4 for 4 h incubation. Source data are provided as a Source Data file.</div> </figcaption> </figure> </div> <!-- Root element of PhotoSwipe. Must have class pswp. --> <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog"> <!-- Background of PhotoSwipe. It's a separate element as animating opacity is faster than rgba(). --> <div class="pswp__bg"></div> <!-- Slides wrapper with overflow:hidden. --> <div class="pswp__scroll-wrap"> <!-- Container that holds slides. PhotoSwipe keeps only 3 of them in the DOM to save memory. Don't modify these 3 pswp__item elements, data is added later on. --> <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div> <!-- Default (PhotoSwipeUI_Default) interface on top of sliding area. Can be changed. --> <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar"> <!-- Controls are self-explanatory. Order can be changed. --> <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button> <!-- Preloader demo http://codepen.io/dimsemenov/pen/yyBWoR --> <!-- element will get class pswp__preloader--active when preloader is running --> <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption"> <!-- Dynamic text --> </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/21474753/" ref="article_id=21474753&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="21474753" data-ga-label=""> Ribozyme-catalyzed transcription of an active ribozyme. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Wochner A, Attwater J, Coulson A, Holliger P.</span> <span class="docsum-authors short-authors">Wochner A, et al.</span> <span class="docsum-journal-citation full-journal-citation">Science. 2011 Apr 8;332(6026):209-12. doi: 10.1126/science.1200752.</span> <span class="docsum-journal-citation short-journal-citation">Science. 2011.</span> <span class="citation-part">PMID: <span class="docsum-pmid">21474753</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/24256864/" ref="article_id=24256864&linksrc=similar_articles_link&ordinalpos=2" data-ga-category="similar_article" data-ga-action="24256864" data-ga-label=""> In-ice evolution of RNA polymerase ribozyme activity. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Attwater J, Wochner A, Holliger P.</span> <span class="docsum-authors short-authors">Attwater J, et al.</span> <span class="docsum-journal-citation full-journal-citation">Nat Chem. 2013 Dec;5(12):1011-8. doi: 10.1038/nchem.1781. Epub 2013 Oct 20.</span> <span class="docsum-journal-citation short-journal-citation">Nat Chem. 2013.</span> <span class="citation-part">PMID: <span class="docsum-pmid">24256864</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/10192287/" ref="article_id=10192287&linksrc=similar_articles_link&ordinalpos=3" data-ga-category="similar_article" data-ga-action="10192287" data-ga-label=""> The antisense sequence of the HIV-1 TAR stem-loop structure covalently linked to the hairpin ribozyme enhances its catalytic activity against two artificial substrates. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Pérez-Ruiz M, Sievers D, García-López PA, Berzal-Herranz A.</span> <span class="docsum-authors short-authors">Pérez-Ruiz M, et al.</span> <span class="docsum-journal-citation full-journal-citation">Antisense Nucleic Acid Drug Dev. 1999 Feb;9(1):33-42. doi: 10.1089/oli.1.1999.9.33.</span> <span class="docsum-journal-citation short-journal-citation">Antisense Nucleic Acid Drug Dev. 1999.</span> <span class="citation-part">PMID: <span class="docsum-pmid">10192287</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/10715200/" ref="article_id=10715200&linksrc=similar_articles_link&ordinalpos=4" data-ga-category="similar_article" data-ga-action="10715200" data-ga-label=""> Structure and function of the hairpin ribozyme. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Fedor MJ.</span> <span class="docsum-authors short-authors">Fedor MJ.</span> <span class="docsum-journal-citation full-journal-citation">J Mol Biol. 2000 Mar 24;297(2):269-91. doi: 10.1006/jmbi.2000.3560.</span> <span class="docsum-journal-citation short-journal-citation">J Mol Biol. 2000.</span> <span class="citation-part">PMID: <span class="docsum-pmid">10715200</span></span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/12573693/" ref="article_id=12573693&linksrc=similar_articles_link&ordinalpos=5" data-ga-category="similar_article" data-ga-action="12573693" data-ga-label=""> In search of an RNA replicase ribozyme. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">McGinness KE, Joyce GF.</span> <span class="docsum-authors short-authors">McGinness KE, et al.</span> <span class="docsum-journal-citation full-journal-citation">Chem Biol. 2003 Jan;10(1):5-14. doi: 10.1016/s1074-5521(03)00003-6.</span> <span class="docsum-journal-citation short-journal-citation">Chem Biol. 2003.</span> <span class="citation-part">PMID: <span class="docsum-pmid">12573693</span></span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> </ul> <div class="actions-bar"> <a class="show-all-linked-articles" data-href="/?linkname=pubmed_pubmed&from_uid=36932102" data-ga-category="similar_article" data-ga-action="show_all" > See all similar articles </a> </div> </div> <div class="citedby-articles" id="citedby"> <h2 class="title"> Cited by </h2> <ul class="articles-list" id="citedby-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/39526332/" ref="article_id=39526332&linksrc=citedby_articles_link&ordinalpos=1" data-ga-category="cited_by" data-ga-action="39526332" data-ga-label=""> Origin of ribonucleotide recognition motifs through ligand mimicry at early earth. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Mozumdar D, Roy RN.</span> <span class="docsum-authors short-authors">Mozumdar D, et al.</span> <span class="docsum-journal-citation full-journal-citation">RNA Biol. 2024 Jan;21(1):107-121. doi: 10.1080/15476286.2024.2423149. Epub 2024 Nov 11.</span> <span class="docsum-journal-citation short-journal-citation">RNA Biol. 2024.</span> <span class="citation-part">PMID: <span class="docsum-pmid">39526332</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> <span class="publication-type spaced-citation-item citation-part">Review.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/38503430/" ref="article_id=38503430&linksrc=citedby_articles_link&ordinalpos=2" data-ga-category="cited_by" data-ga-action="38503430" data-ga-label=""> High-Fidelity RNA Copying via 2',3'-Cyclic Phosphate Ligation. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Calaça Serrão A, Wunnava S, Dass AV, Ufer L, Schwintek P, Mast CB, Braun D.</span> <span class="docsum-authors short-authors">Calaça Serrão A, et al.</span> <span class="docsum-journal-citation full-journal-citation">J Am Chem Soc. 2024 Apr 3;146(13):8887-8894. doi: 10.1021/jacs.3c10813. Epub 2024 Mar 19.</span> <span class="docsum-journal-citation short-journal-citation">J Am Chem Soc. 2024.</span> <span class="citation-part">PMID: <span class="docsum-pmid">38503430</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/38169216/" ref="article_id=38169216&linksrc=citedby_articles_link&ordinalpos=3" data-ga-category="cited_by" data-ga-action="38169216" data-ga-label=""> Constrained dynamics of DNA oligonucleotides in phase-separated droplets. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Singh A, Thutupalli S, Kumar M, Ameta S.</span> <span class="docsum-authors short-authors">Singh A, et al.</span> <span class="docsum-journal-citation full-journal-citation">Biophys J. 2024 Jun 4;123(11):1458-1466. doi: 10.1016/j.bpj.2023.12.025. Epub 2024 Jan 2.</span> <span class="docsum-journal-citation short-journal-citation">Biophys J. 2024.</span> <span class="citation-part">PMID: <span class="docsum-pmid">38169216</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/38096089/" ref="article_id=38096089&linksrc=citedby_articles_link&ordinalpos=4" data-ga-category="cited_by" data-ga-action="38096089" data-ga-label=""> Replication elongates short DNA, reduces sequence bias and develops trimer structure. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Calaça Serrão A, Dänekamp FT, Meggyesi Z, Braun D.</span> <span class="docsum-authors short-authors">Calaça Serrão A, et al.</span> <span class="docsum-journal-citation full-journal-citation">Nucleic Acids Res. 2024 Feb 9;52(3):1290-1297. doi: 10.1093/nar/gkad1190.</span> <span class="docsum-journal-citation short-journal-citation">Nucleic Acids Res. 2024.</span> <span class="citation-part">PMID: <span class="docsum-pmid">38096089</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/37476714/" ref="article_id=37476714&linksrc=citedby_articles_link&ordinalpos=5" data-ga-category="cited_by" data-ga-action="37476714" data-ga-label=""> Minimal RNA self-reproduction discovered from a random pool of oligomers. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Mizuuchi R, Ichihashi N.</span> <span class="docsum-authors short-authors">Mizuuchi R, et al.</span> <span class="docsum-journal-citation full-journal-citation">Chem Sci. 2023 Jun 20;14(28):7656-7664. doi: 10.1039/d3sc01940c. eCollection 2023 Jul 19.</span> <span class="docsum-journal-citation short-journal-citation">Chem Sci. 2023.</span> <span class="citation-part">PMID: <span class="docsum-pmid">37476714</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> </ul> </div> <div class="references" id="references"> <h2 class="title"> References </h2> <div id='top-references-list' class="references-lists-container"> <div class="refs-list"> <ol id="top-references-list-1" class="references-list"> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Gilbert W. Origin of life: the RNA world. Nature. 1986;319:618. doi: 10.1038/319618a0. - <a class="reference-link" href="https://doi.org/10.1038/319618a0" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1038/319618a0" > DOI </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Robertson MP, Joyce GF. The origins of the RNA world. Cold Spring Harb. Perspect. Biol. 2012;4:1. doi: 10.1101/cshperspect.a003608. - <a class="reference-link" href="https://doi.org/10.1101/cshperspect.a003608" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1101/cshperspect.a003608" > DOI </a> - <a class="reference-link" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3331698/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="PMC3331698" > PMC </a> - <a class="reference-link" href="/20739415/" ref="linksrc=references_link&ordinalpos=3" data-ga-category="reference" data-ga-action="20739415" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Joyce GF, Szostak JW. Protocells and RNA Self-Replication. Cold Spring Harb. Perspect. Biol. 2018;10:a034801. doi: 10.1101/cshperspect.a034801. - <a class="reference-link" href="https://doi.org/10.1101/cshperspect.a034801" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1101/cshperspect.a034801" > DOI </a> - <a class="reference-link" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6120706/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="PMC6120706" > PMC </a> - <a class="reference-link" href="/30181195/" ref="linksrc=references_link&ordinalpos=3" data-ga-category="reference" data-ga-action="30181195" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Doudna JA, Couture S, Szostak JW. A multisubunit ribozyme that is a catalyst of and template for complementary strand RNA synthesis. Science. 1991;251:1605–1608. doi: 10.1126/science.1707185. - <a class="reference-link" href="https://doi.org/10.1126/science.1707185" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1126/science.1707185" > DOI </a> - <a class="reference-link" href="/1707185/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="1707185" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Doudna JA, Usman N, Szostak JW. Ribozyme-catalyzed primer extension by trinucleotides: a model for the RNA-catalyzed replication of RNA. Biochemistry. 1993;32:2111–2115. doi: 10.1021/bi00059a032. - <a class="reference-link" href="https://doi.org/10.1021/bi00059a032" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1021/bi00059a032" > DOI </a> - <a class="reference-link" href="/7680575/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="7680575" > PubMed </a> </li> </ol> </li> </ol> <div class="actions-bar"> <button class="show-all" ref="linksrc=show_all_references_link" aria-controls="top-references-list-1" data-next-page-url="/36932102/references/" data-ga-category="reference" data-ga-action="show_more" > Show all 32 references </button> </div> </div> </div> </div> <div id="publication-types" class="publication-types keywords-section"> <h2 class="title"> Publication types </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Research Support, Non-U.S. Gov't" tabindex="0" aria-controls="keyword-actions-publication-types-0" aria-expanded="false" data-pinger-ignore> Research Support, Non-U.S. Gov't </button><div id="keyword-actions-publication-types-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Research Support, Non-U.S. Gov't"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Research+Support%2C+Non-U.S.+Gov%27t%22%5Bpt%5D&sort=date&sort_order=desc" data-href="/?term=%22Research+Support%2C+Non-U.S.+Gov%27t%22%5Bpt%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Research Support, Non-U.S. Gov't"[pt]" data-ga-category="search" data-ga-action="pub_type" data-ga-label="Research Support, Non-U.S. Gov't"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Research+Support%2C+Non-U.S.+Gov%27t" data-ga-category="search_mesh" data-ga-action="pub_type_link" data-ga-label="Research Support, Non-U.S. Gov't"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Research Support, Non-U.S. Gov't"[pt]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Research Support, Non-U.S. Gov't"[pt]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="mesh-terms" class="mesh-terms keywords-section"> <h2 class="title"> MeSH terms </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Base Sequence" tabindex="0" aria-controls="keyword-actions-mesh-terms-0" aria-expanded="false" data-pinger-ignore> Base Sequence </button><div id="keyword-actions-mesh-terms-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Base Sequence"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Base+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Base+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Base Sequence"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Base Sequence"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Base+Sequence" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Base Sequence"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Base Sequence"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Base Sequence"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Nucleic Acid Conformation" tabindex="0" aria-controls="keyword-actions-mesh-terms-1" aria-expanded="false" data-pinger-ignore> Nucleic Acid Conformation </button><div id="keyword-actions-mesh-terms-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Nucleic Acid Conformation"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Nucleic+Acid+Conformation%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Nucleic+Acid+Conformation%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Nucleic Acid Conformation"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Nucleic Acid Conformation"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Nucleic+Acid+Conformation" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Nucleic Acid Conformation"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Nucleic Acid Conformation"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Nucleic Acid Conformation"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA / genetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-2" aria-expanded="false" data-pinger-ignore> RNA / genetics </button><div id="keyword-actions-mesh-terms-2" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA/genetics"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA / genetics"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA / genetics"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA/genetics"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA/genetics"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA / metabolism" tabindex="0" aria-controls="keyword-actions-mesh-terms-3" aria-expanded="false" data-pinger-ignore> RNA / metabolism </button><div id="keyword-actions-mesh-terms-3" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA/metabolism"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA / metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA/metabolism"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA/metabolism"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA, Antisense / genetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-4" aria-expanded="false" data-pinger-ignore> RNA, Antisense / genetics </button><div id="keyword-actions-mesh-terms-4" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Antisense / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Antisense%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Antisense%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA, Antisense/genetics"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA, Antisense / genetics"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA%2C+Antisense" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA, Antisense / genetics"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA, Antisense/genetics"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA, Antisense/genetics"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword RNA, Catalytic* / genetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-5" aria-expanded="false" data-pinger-ignore> RNA, Catalytic* / genetics </button><div id="keyword-actions-mesh-terms-major-5" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Catalytic* / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Catalytic%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Catalytic%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA, Catalytic/genetics"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA, Catalytic* / genetics"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA%2C+Catalytic" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA, Catalytic* / genetics"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA, Catalytic/genetics"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA, Catalytic/genetics"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword RNA, Catalytic* / metabolism" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-6" aria-expanded="false" data-pinger-ignore> RNA, Catalytic* / metabolism </button><div id="keyword-actions-mesh-terms-major-6" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Catalytic* / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Catalytic%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Catalytic%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA, Catalytic/metabolism"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA, Catalytic* / metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA%2C+Catalytic" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA, Catalytic* / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA, Catalytic/metabolism"[MAJR]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA, Catalytic/metabolism"[MAJR]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA-Dependent RNA Polymerase / metabolism" tabindex="0" aria-controls="keyword-actions-mesh-terms-7" aria-expanded="false" data-pinger-ignore> RNA-Dependent RNA Polymerase / metabolism </button><div id="keyword-actions-mesh-terms-7" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA-Dependent RNA Polymerase / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA-Dependent+RNA+Polymerase%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA-Dependent+RNA+Polymerase%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA-Dependent RNA Polymerase/metabolism"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="RNA-Dependent RNA Polymerase / metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=RNA-Dependent+RNA+Polymerase" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="RNA-Dependent RNA Polymerase / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA-Dependent RNA Polymerase/metabolism"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA-Dependent RNA Polymerase/metabolism"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="substances" class="substances keywords-section"> <h2 class="title"> Substances </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA, Catalytic" tabindex="0" aria-controls="keyword-actions-substances-0" aria-expanded="false" data-pinger-ignore> RNA, Catalytic </button><div id="keyword-actions-substances-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Catalytic"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Catalytic%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Catalytic%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="RNA, Catalytic"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="RNA, Catalytic"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22RNA%2C+Catalytic%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="RNA, Catalytic"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA, Catalytic"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA, Catalytic"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA" tabindex="0" aria-controls="keyword-actions-substances-1" aria-expanded="false" data-pinger-ignore> RNA </button><div id="keyword-actions-substances-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="RNA"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="RNA"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22RNA%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="RNA"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA-Dependent RNA Polymerase" tabindex="0" aria-controls="keyword-actions-substances-2" aria-expanded="false" data-pinger-ignore> RNA-Dependent RNA Polymerase </button><div id="keyword-actions-substances-2" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA-Dependent RNA Polymerase"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA-Dependent+RNA+Polymerase%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA-Dependent+RNA+Polymerase%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="RNA-Dependent RNA Polymerase"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="RNA-Dependent RNA Polymerase"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22RNA-Dependent+RNA+Polymerase%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="RNA-Dependent RNA Polymerase"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA-Dependent RNA Polymerase"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA-Dependent RNA Polymerase"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword RNA, Antisense" tabindex="0" aria-controls="keyword-actions-substances-3" aria-expanded="false" data-pinger-ignore> RNA, Antisense </button><div id="keyword-actions-substances-3" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword RNA, Antisense"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22RNA%2C+Antisense%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22RNA%2C+Antisense%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="RNA, Antisense"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="RNA, Antisense"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22RNA%2C+Antisense%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="RNA, Antisense"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""RNA, Antisense"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""RNA, Antisense"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="related-links" class="related-links"> <h2 class="title"> Related information </h2> <ul class="related-links-list"><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=36932102" ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=36932102&ordinalpos=1&linkpos=1"> MedGen </a></li></ul> </div> <div id="linkout" class="linkout"> <h2 class="title"> LinkOut - more resources </h2> <ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a href="https://europepmc.org/abstract/MED/36932102" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=6082&uid=36932102&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=101528555" data-ga-category="link_out" data-ga-action="Full Text Sources" data-ga-label="Europe PubMed Central" > Europe PubMed Central </a></li><li><a href="https://doi.org/10.1038/s41467-023-37206-4" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=3094&uid=36932102&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=101528555" data-ga-category="link_out" data-ga-action="Full Text Sources" data-ga-label="Nature Publishing Group" > Nature Publishing Group </a></li><li><a href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/36932102/" target="_blank" rel="noopener" ref="linksrc=linkout_link&PrId=3494&uid=36932102&db=pubmed&itool=Abstract&log$=linkoutlink&nlmid=101528555" data-ga-category="link_out" data-ga-action="Full Text Sources" data-ga-label="PubMed Central" > PubMed Central </a></li></ul></li></ul> </div> </main> <div class="overlay" role="dialog" aria-label="Full Text Links Dialog"> <div id="full-text-links-dialog" class="dialog full-text-links-dialog"> <strong class="title">Full text links</strong> <button class="close-overlay" tabindex="3">[x]</button> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://doi.org/10.1038/s41467-023-37206-4" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3094&itool=Abstract-def&log$=linkouticon&uid=36932102&db=pubmed&nlmid=101528555" title="See full text options at Nature Publishing Group" tabindex="1" data-ga-category="full_text" data-ga-action="Nature Publishing Group" data-ga-label="36932102" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.nature.com-static-images-logos-nature-portfolio-120.png" alt="full text provider logo"><span class="text"> Nature Publishing Group </span></a><a class="link-item pmc " href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/36932102/" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=36932102&db=pubmed&nlmid=101528555" title="Free full text at PubMed Central" tabindex="2" data-ga-category="full_text" data-ga-action="PMC" data-ga-label="36932102" ><span class="text"> Free PMC article </span></a> </div> </div> </div> <div class="overlay" role="dialog" aria-label="Citation Dialog"> <div class="dialog citation-dialog"> <button class="close-overlay" tabindex="1">[x]</button> <div class="title">Cite</div> <div class="citation-text-block"> <div class="citation-text"></div> <div class="citation-actions"> <button class="copy-button dialog-focus" data-ga-category="save_share" data-ga-action="cite" data-ga-label="copy" tabindex="2"> Copy </button> <form method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="zOisrQVLcS4bxKQHpNCSKlKBiJWFAQ6o7SoyMWmf1jtnW4DfNu7G9ET8VwojQ7CC"> <button type="submit" class="export-button" data-ga-category="save_share" data-ga-action="cite" data-ga-label="download" title="Download a file for external citation management software" tabindex="3"> <span class="download-title">Download .nbib</span> <span class="download-title-mobile">.nbib</span> </button> </form> <div class="citation-style-selector-wrapper"> <label class="selector-label">Format:</label> <select aria-label="Format" class="citation-style-selector" tabindex="4"> <option data-style-url-name="ama" value="AMA" > AMA </option> <option data-style-url-name="apa" value="APA" > APA </option> <option data-style-url-name="mla" value="MLA" > MLA </option> <option data-style-url-name="nlm" value="NLM" selected="selected"> NLM </option> </select> </div> </div> </div> </div> </div> <div class="overlay" role="dialog" aria-label="More Actions Dialog"> <div id="more-actions-dialog" class="dialog more-actions-dialog"> <strong class="title">Send To</strong> <ul class="more-actions-links"> <li><a id="clipboard-trigger" role="button" class="submit-button clipboard-trigger clipboard-trigger-target dialog-focus link-item " href="#">Clipboard</a></li> <li><a class="email-trigger link-item" role="button" href="#">Email</a></li> <li><a class="save-trigger link-item" role="button" href="#">Save</a></li> <li><a class="link-item" role="button" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36932102%2F%23open-bibliography-panel">My Bibliography</a></li> <li><a class="link-item" role="button" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36932102%2F%23open-collections-panel">Collections</a></li> <li><a class="citation-manager-trigger link-item" role="button" href="#">Citation Manager</a></li> </ul> <button class="close-overlay">[x]</button> </div> </div> </div> <div id="ncbi-footer"> <div class="literature-footer" role="complementary" title="Links to NCBI Literature Resources"> <div class="usa-grid"> <p class="literature-footer-text">NCBI Literature Resources</p> <p class="literature-footer-text"> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh/">MeSH</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="pmc_link" href="https://www.ncbi.nlm.nih.gov/pmc/">PMC</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="bookshelf_link" href="https://www.ncbi.nlm.nih.gov/books">Bookshelf</a> <a class="literature-footer-link" data-ga-category="literature_resources" data-ga-action="disclaimer_link" href="/disclaimer/">Disclaimer</a> </p> <p class="literature-footer-text attribution-statement">The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.</p> </div> </div> <!-- ========== BEGIN FOOTER ========== --> <footer> <section class="icon-section"> <div id="icon-section-header" class="icon-section_header">Follow NCBI</div> <div class="grid-container container"> <div class="icon-section_container"> <a class="footer-icon" id="footer_twitter" href="https://twitter.com/ncbi" aria-label="Twitter"> <svg width="40" height="40" viewBox="0 0 40 37" fill="none" xmlns="http://www.w3.org/2000/svg"> <title>Twitter</title> <g id="twitterx1008"> <path id="path1008" d="M6.06736 7L16.8778 20.8991L6.00001 32.2H10.2L18.6 23.1L25.668 32.2H34L22.8 17.5L31.9 7H28.4L20.7 15.4L14.401 7H6.06898H6.06736ZM9.66753 8.73423H12.9327L29.7327 30.4658H26.5697L9.66753 8.73423Z" fill="#5B616B"/> </g> </svg> </a> <a class="footer-icon" id="footer_facebook" href="https://www.facebook.com/ncbi.nlm" aria-label="Facebook"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <title>Facebook</title> <path class="cls-11" d="M210.5,115.12H171.74V97.82c0-8.14,5.39-10,9.19-10h27.14V52l-39.32-.12c-35.66,0-42.42,26.68-42.42,43.77v19.48H99.09v36.32h27.24v109h45.41v-109h35Z"> </path> </svg></a> <a class="footer-icon" id="footer_linkedin" href="https://www.linkedin.com/company/ncbinlm" aria-label="LinkedIn"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <title>LinkedIn</title> <path class="cls-11" d="M101.64,243.37H57.79v-114h43.85Zm-22-131.54h-.26c-13.25,0-21.82-10.36-21.82-21.76,0-11.65,8.84-21.15,22.33-21.15S101.7,78.72,102,90.38C102,101.77,93.4,111.83,79.63,111.83Zm100.93,52.61A17.54,17.54,0,0,0,163,182v61.39H119.18s.51-105.23,0-114H163v13a54.33,54.33,0,0,1,34.54-12.66c26,0,44.39,18.8,44.39,55.29v58.35H198.1V182A17.54,17.54,0,0,0,180.56,164.44Z"> </path> </svg></a> <a class="footer-icon" id="footer_github" href="https://github.com/ncbi" aria-label="GitHub"><svg data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 300 300"> <defs> <style> .cls-11, .cls-12 { fill: #737373; } .cls-11 { fill-rule: evenodd; } </style> </defs> <title>GitHub</title> <path class="cls-11" d="M151.36,47.28a105.76,105.76,0,0,0-33.43,206.1c5.28,1,7.22-2.3,7.22-5.09,0-2.52-.09-10.85-.14-19.69-29.42,6.4-35.63-12.48-35.63-12.48-4.81-12.22-11.74-15.47-11.74-15.47-9.59-6.56.73-6.43.73-6.43,10.61.75,16.21,10.9,16.21,10.9,9.43,16.17,24.73,11.49,30.77,8.79,1-6.83,3.69-11.5,6.71-14.14C108.57,197.1,83.88,188,83.88,147.51a40.92,40.92,0,0,1,10.9-28.39c-1.1-2.66-4.72-13.42,1-28,0,0,8.88-2.84,29.09,10.84a100.26,100.26,0,0,1,53,0C198,88.3,206.9,91.14,206.9,91.14c5.76,14.56,2.14,25.32,1,28a40.87,40.87,0,0,1,10.89,28.39c0,40.62-24.74,49.56-48.29,52.18,3.79,3.28,7.17,9.71,7.17,19.58,0,14.15-.12,25.54-.12,29,0,2.82,1.9,6.11,7.26,5.07A105.76,105.76,0,0,0,151.36,47.28Z"> </path> <path class="cls-12" d="M85.66,199.12c-.23.52-1.06.68-1.81.32s-1.2-1.06-.95-1.59,1.06-.69,1.82-.33,1.21,1.07.94,1.6Zm-1.3-1"> </path> <path class="cls-12" d="M90,203.89c-.51.47-1.49.25-2.16-.49a1.61,1.61,0,0,1-.31-2.19c.52-.47,1.47-.25,2.17.49s.82,1.72.3,2.19Zm-1-1.08"> </path> <path class="cls-12" d="M94.12,210c-.65.46-1.71,0-2.37-.91s-.64-2.07,0-2.52,1.7,0,2.36.89.65,2.08,0,2.54Zm0,0"></path> <path class="cls-12" d="M99.83,215.87c-.58.64-1.82.47-2.72-.41s-1.18-2.06-.6-2.7,1.83-.46,2.74.41,1.2,2.07.58,2.7Zm0,0"> </path> <path class="cls-12" d="M107.71,219.29c-.26.82-1.45,1.2-2.64.85s-2-1.34-1.74-2.17,1.44-1.23,2.65-.85,2,1.32,1.73,2.17Zm0,0"> </path> <path class="cls-12" d="M116.36,219.92c0,.87-1,1.59-2.24,1.61s-2.29-.68-2.3-1.54,1-1.59,2.26-1.61,2.28.67,2.28,1.54Zm0,0"> </path> <path class="cls-12" d="M124.42,218.55c.15.85-.73,1.72-2,1.95s-2.37-.3-2.52-1.14.73-1.75,2-2,2.37.29,2.53,1.16Zm0,0"></path> </svg></a> <a class="footer-icon" id="footer_blog" href="https://ncbiinsights.ncbi.nlm.nih.gov/" aria-label="Blog"> <svg id="Layer_1" data-name="Layer 1" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 40"><defs><style>.cls-1{fill:#737373;}</style></defs><path class="cls-1" d="M14,30a4,4,0,1,1-4-4,4,4,0,0,1,4,4Zm11,3A19,19,0,0,0,7.05,15a1,1,0,0,0-1,1v3a1,1,0,0,0,.93,1A14,14,0,0,1,20,33.07,1,1,0,0,0,21,34h3a1,1,0,0,0,1-1Zm9,0A28,28,0,0,0,7,6,1,1,0,0,0,6,7v3a1,1,0,0,0,1,1A23,23,0,0,1,29,33a1,1,0,0,0,1,1h3A1,1,0,0,0,34,33Z"/></svg> </a> </div> </div> </section> <section class="container-fluid bg-primary"> <div class="container pt-5"> <div class="row mt-3"> <div class="col-lg-3 col-12"> <p><a class="text-white" href="https://www.nlm.nih.gov/socialmedia/index.html">Connect with NLM</a></p> <ul class="list-inline social_media"> <li class="list-inline-item"><a href="https://twitter.com/NLM_NIH" aria-label="Twitter" target="_blank" rel="noopener noreferrer"> <svg width="35" height="35" viewBox="0 0 38 35" fill="none" xmlns="http://www.w3.org/2000/svg"> <title>Twitter</title> <g id="twitterx1009" clip-path="url(#clip0_65276_3946)"> <path id="Vector" d="M17.5006 34.6565C26.9761 34.6565 34.6575 26.9751 34.6575 17.4996C34.6575 8.02416 26.9761 0.342773 17.5006 0.342773C8.02514 0.342773 0.34375 8.02416 0.34375 17.4996C0.34375 26.9751 8.02514 34.6565 17.5006 34.6565Z" fill="#205493" stroke="white" stroke-width="1.2" stroke-miterlimit="10"></path> <path id="path1009" d="M8.54811 8.5L16.2698 18.4279L8.50001 26.5H11.5L17.5 20L22.5486 26.5H28.5L20.5 16L27 8.5H24.5L19 14.5L14.5007 8.5H8.54927H8.54811ZM11.1197 9.73873H13.4519L25.4519 25.2613H23.1926L11.1197 9.73873Z" fill="white"></path> </g> <defs> <clipPath id="clip0_65276_3946"> <rect width="38" height="38" fill="white"></rect> </clipPath> </defs> </svg></a> </li> <li class="list-inline-item"><a href="https://www.facebook.com/nationallibraryofmedicine" aria-label="Facebook" rel="noopener noreferrer" target="_blank"> <svg version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve"> <style type="text/css"> .st10 { fill: #FFFFFF; } .st110 { fill: none; stroke: #FFFFFF; stroke-width: 8; stroke-miterlimit: 10; } </style> <title>SM-Facebook</title> <g> <g> <path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path> </g> </g> <circle class="st110" cx="123.6" cy="123.2" r="108.2"></circle> </svg> </a></li> <li class="list-inline-item"><a href="https://www.youtube.com/user/NLMNIH" aria-label="Youtube" target="_blank" rel="noopener noreferrer"><svg version="1.1" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve"> <title>SM-Youtube</title> <style type="text/css"> .st4 { fill: none; stroke: #FFFFFF; stroke-width: 8; stroke-miterlimit: 10; } .st5 { fill: #FFFFFF; } </style> <circle class="st4" cx="124.2" cy="123.4" r="108.2"></circle> <g transform="translate(0,-952.36218)"> <path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path> </g> </svg></a></li> </ul> </div> <div class="col-lg-3 col-12"> <p class="address_footer text-white">National Library of Medicine<br> <a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br> Bethesda, MD 20894</a></p> </div> <div class="col-lg-3 col-12 centered-lg"> <p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br> <a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br> <a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p> </div> <div class="col-lg-3 col-12 centered-lg"> <p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br> <a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br> <a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p> </div> </div> <div class="row"> <div class="col-lg-12 centered-lg"> <nav class="bottom-links"> <ul class="mt-3"> <li> <a class="text-white" href="//www.nlm.nih.gov/">NLM</a> </li> <li> <a class="text-white" href="https://www.nih.gov/">NIH</a> </li> <li> <a class="text-white" href="https://www.hhs.gov/">HHS</a> </li> <li> <a class="text-white" href="https://www.usa.gov/">USA.gov</a> </li> </ul> </nav> </div> </div> </div> </section> </footer> <!-- ========== END FOOTER ========== --> <!-- javascript to inject NWDS meta tags. Note: value of nwds_version is updated by "npm version" command --> <script type="text/javascript"> var nwds_version = "1.2.3"; var meta_nwds_ver = document.createElement('meta'); meta_nwds_ver.name = 'ncbi_nwds_ver'; meta_nwds_ver.content = nwds_version; document.getElementsByTagName('head')[0].appendChild(meta_nwds_ver); var meta_nwds = document.createElement('meta'); meta_nwds.name = 'ncbi_nwds'; meta_nwds.content = 'yes'; document.getElementsByTagName('head')[0].appendChild(meta_nwds); var alertsUrl = "/core/alerts/alerts.js"; if (typeof ncbiBaseUrl !== 'undefined') { alertsUrl = ncbiBaseUrl + alertsUrl; } </script> </div> <!-- jQuery with plugins --> <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/js/output.293fbf76aa18.js"></script> <!-- Project base scripts --> <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/js/output.550e9c8906a2.js"></script> <script> ncbi.awesome.basePage.init({ userInfo: { isLoggedIn: false, username: "", loginUrl: "https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36932102%2F", logoutUrl: "https://www.ncbi.nlm.nih.gov/account/signout/?back_url=https%3A//pubmed.ncbi.nlm.nih.gov/36932102/" }, baseUrl: 'https://www.ncbi.nlm.nih.gov', noSessionCookieName: "pm-ns", searchIdCookieName: "pm-sid", adjNavSearchIdCookieName: "pm-adjnav-sid", searchFormSubmittedCookieName: "pm-sfs", isOnSearchPageCookieName: "pm-iosp", backToSearchCookieName: "pm-btsl", clinicalSeeAllCookieName: "pm-csa", jsCookieDomain: "pubmed.ncbi.nlm.nih.gov", userShareRequestFailed: "", noSharedSettings: "myncbi_no_shared_settings", noSharedAccount: "myncbi_no_shared_account" }); </script> <script type="module"> import dismissableNCBIAlert from "https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/dismissable-ncbi-alert.js"; jQuery.getScript("https://www.ncbi.nlm.nih.gov/core/alerts/alerts.js", function () { galert(['body > *:last-child']); dismissableNCBIAlert(); }).fail(function() { }); </script> <script defer type="text/javascript" src="https://cdn.ncbi.nlm.nih.gov/core/pinger/pinger.js"> </script> <script src="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/CACHE/js/output.04d45d85d031.js"></script> <script> ncbi.awesome.articlePage.init({ baseSuggestionsUrl: "/suggestions/", mathJaxUrl: "https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/mathjax/unpacked/MathJax.js?config=MML_CHTML", clipboardAPIRoot: "/ajax/clipboard/", clipboardNextPageUrl: "/clipboard-next-page/", searchIdCookieName: "pm-sid", searchFormSubmittedCookieName: "pm-sfs", backToSearchCookieName: "pm-btsl", jsCookieDomain: "pubmed.ncbi.nlm.nih.gov", longTermPrefix: "longquery", adjNavURLPath: "/36932102/adj-nav/", adjNavSearchIdCookieName: "pm-adjnav-sid", articlePageUrl: "/36932102/", markJSUrl: "https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/mark.js/dist/jquery.mark.js", termHighlightColor: "", highlightedTokens: "", citeFormatPreferenceCookieName: "pm-cf" }); </script> </body> </html>