CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III

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Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders. CRISPR is a microbial RNA-based immune system protecting against viral and plasmid invasions. The CRISPR system is thought to rely on cleavage of a precursor RNA transcript by Cas endonucleases, but not all species with CRISPR-type immunity encode Cas proteins. A new study reveals an alternative pathway for CRISPR activation in the human pathogen Streptococcus pyogenes, in which a trans-encoded small RNA directs processing of precursor RNA into crRNAs through endogenous RNase III and the CRISPR-associated Csn1 protein. CRISPR is a microbial RNA-based immune system protecting against viral and plasmid invasions. The CRISPR system is thought to rely on cleavage of a precursor RNA transcript by Cas endonucleases, but not all species possessing CRISPR-type immunity encode Cas proteins. 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The CRISPR system is thought to rely on cleavage of a precursor RNA transcript by Cas..."/> <meta name="twitter:image" content="https://media.springernature.com/full/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig1_HTML.jpg"/> <meta property="og:url" content="https://www.nature.com/articles/nature09886"/> <meta property="og:type" content="article"/> <meta property="og:site_name" content="Nature"/> <meta property="og:title" content="CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III - Nature"/> <meta property="og:description" content="CRISPR is a microbial RNA-based immune system protecting against viral and plasmid invasions. The CRISPR system is thought to rely on cleavage of a precursor RNA transcript by Cas endonucleases, but not all species possessing CRISPR-type immunity encode Cas proteins. 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itemscope itemtype="https://schema.org/ListItem"> <span itemprop="name">article</span><meta itemprop="position" content="3"></li> </ol> </div> </nav> </div> <div class="u-container u-mt-32 u-mb-32 u-clearfix" id="content" data-component="article-container" data-container-type="article"> <main class="c-article-main-column u-float-left js-main-column" data-track-component="article body"> <article lang="en"> <div class="c-article-header"> <header> <ul class="c-article-identifiers" data-test="article-identifier"> <li class="c-article-identifiers__item" data-test="article-category">Article</li> <li class="c-article-identifiers__item">Published: <time datetime="2011-03-30">30 March 2011</time></li> </ul> <h1 class="c-article-title" data-test="article-title" data-article-title="">CRISPR RNA maturation by <i>trans</i>-encoded small RNA and host factor RNase III</h1> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Elitza-Deltcheva-Aff1-Aff2" data-author-popup="auth-Elitza-Deltcheva-Aff1-Aff2" data-author-search="Deltcheva, Elitza">Elitza Deltcheva</a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Krzysztof-Chylinski-Aff1-Aff2" data-author-popup="auth-Krzysztof-Chylinski-Aff1-Aff2" data-author-search="Chylinski, Krzysztof">Krzysztof Chylinski</a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a></sup><sup class="u-js-hide"> <a href="#na1">na1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Cynthia_M_-Sharma-Aff3" data-author-popup="auth-Cynthia_M_-Sharma-Aff3" data-author-search="Sharma, Cynthia M.">Cynthia M. Sharma</a><sup class="u-js-hide"><a href="#Aff3">3</a></sup><sup class="u-js-hide"> <a href="#na1">na1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Karine-Gonzales-Aff2" data-author-popup="auth-Karine-Gonzales-Aff2" data-author-search="Gonzales, Karine">Karine Gonzales</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Yanjie-Chao-Aff3-Aff4" data-author-popup="auth-Yanjie-Chao-Aff3-Aff4" data-author-search="Chao, Yanjie">Yanjie Chao</a><sup class="u-js-hide"><a href="#Aff3">3</a>,<a href="#Aff4">4</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Zaid_A_-Pirzada-Aff2" data-author-popup="auth-Zaid_A_-Pirzada-Aff2" data-author-search="Pirzada, Zaid A.">Zaid A. Pirzada</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Maria_R_-Eckert-Aff2" data-author-popup="auth-Maria_R_-Eckert-Aff2" data-author-search="Eckert, Maria R.">Maria R. Eckert</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-J_rg-Vogel-Aff3-Aff4" data-author-popup="auth-J_rg-Vogel-Aff3-Aff4" data-author-search="Vogel, Jörg">Jörg Vogel</a><sup class="u-js-hide"><a href="#Aff3">3</a>,<a href="#Aff4">4</a></sup> & </li><li class="c-article-author-list__show-more" aria-label="Show all 9 authors for this article" title="Show all 9 authors for this article">…</li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Emmanuelle-Charpentier-Aff1-Aff2" data-author-popup="auth-Emmanuelle-Charpentier-Aff1-Aff2" data-author-search="Charpentier, Emmanuelle" data-corresp-id="c1">Emmanuelle Charpentier<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a></sup> </li></ul><button aria-expanded="false" class="c-article-author-list__button"><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-down-medium"></use></svg><span>Show authors</span></button> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Nature</i></a> <b data-test="journal-volume"><span class="u-visually-hidden">volume</span> 471</b>, <span class="u-visually-hidden">pages </span>602–607 (<span data-test="article-publication-year">2011</span>)<a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">73k <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="citation-count"> <p class="c-article-metrics-bar__count">1755 <span class="c-article-metrics-bar__label">Citations</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">324 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/nature09886/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </header> <div class="u-js-hide" data-component="article-subject-links"> <h3 class="c-article__sub-heading">Subjects</h3> <ul class="c-article-subject-list"> <li class="c-article-subject-list__subject"><a href="/subjects/bacterial-physiology" data-track="click" data-track-action="view subject" data-track-label="link">Bacterial physiology</a></li><li class="c-article-subject-list__subject"><a href="/subjects/pathogens" data-track="click" data-track-action="view subject" data-track-label="link">Pathogens</a></li><li class="c-article-subject-list__subject"><a href="/subjects/rna-metabolism" data-track="click" data-track-action="view subject" data-track-label="link">RNA metabolism</a></li> </ul> </div> </div> <div class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen <i>Streptococcus pyogenes</i> uncovered tracrRNA, a <i>trans</i>-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect <i>S. pyogenes</i> against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.</p></div></div></section> <noscript> <div class="c-nature-box c-nature-box--side " data-component="entitlement-box"> <div class="js-access-button"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fnature09886" class="c-article__button" data-test="ra21"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-buy-button"> <a href="#access-options" class="c-article__button c-article__button--inverted" data-test="ra21"> <span>Buy or subscribe</span> </a> </div> </div> </noscript> <div class="js-context-bar-sticky-point-mobile" data-track-context="article body"> </div> <div 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data-track-label="link">Contact customer support</a> </li> </ul> </nav> <div class="u-display-none"> <div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-1"><figure><figcaption><b id="Fig1" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 1: <b>A newly identified tracrRNA is required for crRNA maturation in </b> <b><i>S. pyogenes</i></b>.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig1_HTML.jpg?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig1_HTML.jpg" alt="" loading="lazy" width="312" height="223"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-2"><figure><figcaption><b id="Fig2" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 2: <b>Co-processing of tracrRNA and pre-crRNA requires both endogenous RNase III and Csn1 </b> <b><i>in vivo</i></b>.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig2_HTML.jpg?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig2_HTML.jpg" alt="" loading="lazy" width="202" height="312"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-3"><figure><figcaption><b id="Fig3" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 3: <b>tracrRNA directs pre-crRNA cleavage by RNase III </b> <b><i>in vitro</i></b>.</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig3_HTML.jpg?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig3_HTML.jpg" alt="" loading="lazy" width="312" height="233"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-4"><figure><figcaption><b id="Fig4" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 4: <b>Model for tracrRNA-mediated crRNA maturation involving RNase III and Csn1.</b> </b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig4_HTML.jpg?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig4_HTML.jpg" alt="" loading="lazy" width="312" height="232"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-5"><figure><figcaption><b id="Fig5" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 5: <b>Both tracrRNA and pre-crRNA confer immunity against acquisition of a protospacer gene derived from a lysogenic phage.</b> </b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><picture><source type="image/webp" srcset="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig5_HTML.jpg?as=webp"><img src="//media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_Article_BFnature09886_Fig5_HTML.jpg" alt="" loading="lazy" width="312" height="234"></picture></div></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-6"><figure><figcaption><b id="Fig6" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 6: <b>tracrRNA-mediated crRNA maturation is conserved among different bacterial species.</b> </b></figcaption><div 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id="Bib1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Bib1">References</h2><div class="c-article-section__content" id="Bib1-content"><div data-container-section="references"><ol class="c-article-references" data-track-component="outbound reference" data-track-context="references section"><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="1"><p class="c-article-references__text" id="ref-CR1">Aliyari, R. & Ding, S. 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Veit for technical help. This work was funded by the European Community (FP6, BACRNAs-018618; E.C.), the Austrian Science Fund (FWF, P17238-B09 (E.C.) and W1207-B09 (E.C., K.C.)), the Austrian Agency for Research Promotion (FFG, 812138-SCK/KUG; E.C.), the Theodor Körner Fonds (E.C.), Umeå University (E.C.), the Swedish Research Council (E.C.), IMPRS-IDI (Y.C.), the German Research Council (DFG Priority Program “Sensory and Regulatory RNAs in Prokaryotes” SPP1258, Vo875/4; J.V.), and the German Ministry of Education and Research (BMBF, 01GS0806/JV-BMBF-01 and 0315836; J.V.).</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><span class="c-article-author-information__subtitle u-visually-hidden" id="author-notes">Author notes</span><ol class="c-article-author-information__list"><li class="c-article-author-information__item" id="na1"><p>Krzysztof Chylinski and Cynthia M. Sharma: These authors contributed equally to this work.</p></li></ol><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Department of Molecular Biology, The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Umeå University, S-90187 Umeå, Sweden, </p><p class="c-article-author-affiliation__authors-list">Elitza Deltcheva, Krzysztof Chylinski & Emmanuelle Charpentier</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria, </p><p class="c-article-author-affiliation__authors-list">Elitza Deltcheva, Krzysztof Chylinski, Karine Gonzales, Zaid A. Pirzada, Maria R. Eckert & Emmanuelle Charpentier</p></li><li id="Aff3"><p class="c-article-author-affiliation__address">ZINF Research Center for Infectious Diseases, University of Würzburg, D-97080 Würzburg, Germany, </p><p class="c-article-author-affiliation__authors-list">Cynthia M. Sharma, Yanjie Chao & Jörg Vogel</p></li><li id="Aff4"><p class="c-article-author-affiliation__address">RNA Biology Group, Institute for Molecular Infection Biology, University of Würzburg, D-97080 Würzburg, Germany, </p><p class="c-article-author-affiliation__authors-list">Yanjie Chao & Jörg Vogel</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Elitza-Deltcheva-Aff1-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">Elitza Deltcheva</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Elitza%20Deltcheva" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Elitza%20Deltcheva" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Elitza%20Deltcheva%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Krzysztof-Chylinski-Aff1-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">Krzysztof Chylinski</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Krzysztof%20Chylinski" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Krzysztof%20Chylinski" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Krzysztof%20Chylinski%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Cynthia_M_-Sharma-Aff3"><span class="c-article-authors-search__title u-h3 js-search-name">Cynthia M. 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Author information and raw data are available from E.D., K.C., C.M.S., J.V. and E.C.</p><h3 class="c-article__sub-heading" id="corresponding-author">Corresponding author</h3><p id="corresponding-author-list">Correspondence to <a id="corresp-c1" href="mailto:emmanuelle.charpentier@mims.umu.se">Emmanuelle Charpentier</a>.</p></div></div></section><section data-title="Ethics declarations"><div class="c-article-section" id="ethics-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="ethics">Ethics declarations</h2><div class="c-article-section__content" id="ethics-content"> <h3 class="c-article__sub-heading">Competing interests</h3> <p>The authors declare no competing financial interests.</p> </div></div></section><section data-title="Supplementary information"><div class="c-article-section" id="Sec25-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec25">Supplementary information</h2><div class="c-article-section__content" id="Sec25-content"><div data-test="supplementary-info"><div id="figshareContainer" class="c-article-figshare-container" data-test="figshare-container"></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM302"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figures" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_BFnature09886_MOESM302_ESM.pdf" data-supp-info-image="">Supplementary Figures</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>This file contains Supplementary Figures 1-17 with legends and additional references. (PDF 3511 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM303"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary tables" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature09886/MediaObjects/41586_2011_BFnature09886_MOESM303_ESM.pdf" data-supp-info-image="">Supplementary Tables</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>This file contains Supplementary Tables 1-10 and additional references. 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CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III | Nature