Non-Coding RNA Research and Technologies

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<li data-node-id="326160" data-node-publishdate="1728317220" class="b-post js-post js-comment-entry__parent list-item list-item-text h-left h-clear conversation-starter js-conversation-starter" itemscope itemtype="http://schema.org/Article"> <meta itemprop="name" content="Non-Coding RNA Research and Technologies" /> <meta itemprop="url" content="https://www.seqanswers.com/articles/326160-non-coding-rna-research-and-technologies" /> <a id="post326160" class="anchor"></a> <div class="b-post__hide-when-deleted"> <hr class="b-divider--section">  <div class="js-post__content-wrapper list-item-body-wrapper h-clear" data-node-type="starter"> <div class="js-post__content list-item-body conversation-body"> <div class="axd axd_first-post"> </div> <h2 class="b-post__stream-post-title js-post-title h-hide">Non-Coding RNA Research and Technologies</h2> <div class="post-content restore js-post__content-text h-wordwrap" itemprop="text"> <div class="img_align_center_wrapper"><img alt="Click image for larger version Name: RNA image2.jpg Views: 0 Size: 70.3 KB ID: 326161" title="RNA image2.jpg" data-attachmentid="326161" width="800" height="228" data-align="center" border="0" src="filedata/fetch?id=326161&d=1728317091" data-fullsize-url="filedata/fetch?id=326161&d=1728317091" data-thumb-url="filedata/fetch?id=326161&d=1728317091&type=thumb" data-title="Click on the image to see the original version" data-caption="RNA image2.jpg" class="bbcode-attachment align_center js-lightbox bbcode-attachment--lightbox" /></div><br /> <br /> <br /> <br /> Non-coding RNAs (ncRNAs) do not code for proteins but play important roles in numerous cellular processes including gene silencing, developmental pathways, and more. There are numerous types including microRNA (miRNA), long ncRNA (lncRNA), circular RNA (circRNA), and more. In this article, we discuss innovative ncRNA research and explore recent technological advancements that improve the study of ncRNAs.<br /> <br /> <span style="font-size:16px"><b>Nobel Prize for MicroRNA Discovery</b></span><br /> This week, Victor Ambros and Gary Ruvkun were awarded the 2024 Nobel Prize in Physiology or Medicine for their discovery of microRNA and its role in controlling gene activity. MicroRNAs are small RNA molecules that regulate gene expression after transcription<sup>1</sup>. Ambros and Ruvkun’s research on <i>C. elegans</i> led to the identification of lin-4, a gene producing a short RNA molecule that regulates another gene, lin-14, by blocking its protein production<sup>2,3</sup>. This discovery introduced a new understanding of gene regulation, showing that microRNAs bind to complementary sequences in mRNA and prevent protein synthesis. Their work was initially met with skepticism, but several years later, another microRNA, let-7, was identified and found to be highly conserved across species. This helped establish the acceptance of microRNA regulation in multicellular organisms. Ambros and Ruvkun's breakthroughs helped scientists understand new ways genes are regulated after transcription, revealing a key process that is integral to complex life forms.<br /> <br /> <b><span style="font-size:16px">X Chromosome Inactivation and Autoimmunity</span></b><br /> Another expert studying the impact of important ncRNAs is Montserrat C. Anguera Ph.D., Associate Professor in the Department of Biomedical Sciences at the University of Pennsylvania School of Veterinary Medicine. Anguera's lab is largely focused on studying X chromosome inactivation (XCI) in the immune system. "We want to understand how the X chromosome —both the genetics and the epigenetics of the X chromosome—contributes to female bias diseases that involve the immune system,” stated Anguera. Historically, sex hormones were thought to explain this difference, but Anguera's group is studying how gene expression may play an important role.<br /> <br /> During XCI, one of the two X chromosomes in XX individuals is silenced to balance gene expression. This process is heavily dependent on Xist, a long non-coding RNA (lncRNA). “Xist is really a fascinating RNA molecule because it works in cis, and it can transcriptionally silence most of the chromosome from where it's expressed,” explained Anguera. In particular, it silences most of the X chromosome by recruiting proteins and adding epigenetic modifications that ensure the silenced X remains inactive. However, Anguera's lab discovered that some immune cells, like T cells and B cells, do not always maintain the typical markers of XCI seen in other cell types<sup>4</sup>. In these immune cells, Xist is expressed but it does not localize to the inactive X chromosome, and heterochromatic marks that typically overlap with Xist RNA are absent. "It's almost like the inactive X is not as tightly compact and it's amenable for parts of it to get reactivated in these immune cells, if necessary," noted Anguera. These findings suggest that partial reactivation of the inactive X could contribute to females' heightened immune response and increased susceptibility to autoimmune disorders like lupus.<br /> <br /> Since her landmark study into this process, Anguera has continued investigating the role of Xist deletion in B cells and its connection to the development of systemic lupus erythematosus (SLE)<sup>5</sup>. After developing a mouse model with B cell-specific deletion of the Xist gene, Anguera’s group observed that some female mice with this deletion spontaneously developed SLE-like symptoms, such as the production of disease-specific autoantibodies, glomerulonephritis, and expansion of activated B cell subsets. Furthermore, the severity of SLE-like disease increased in these mice when exposed to pristane, a chemical that induces lupus-like symptoms. The study demonstrated that impaired XCI in B cells can contribute to the female bias observed in SLE by upregulating proinflammatory X-linked genes, such as <i>Tasl</i>, a key component of the TLR7 signaling pathway linked to SLE pathogenesis.<br /> <br /> In another recent study, the lab explored the role of NF-κB signaling in maintaining X chromosome inactivation in T cells following activation<sup>6</sup>. They revealed that the inactive X chromosome in unstimulated T cells is mostly dosage-compensated with specific epigenetic modifications, particularly H3K27me3, but lacks others like H2AK119-ubiquitin. After T cell activation, these marks accumulate, and NF-κB signaling, triggered through T cell receptor (TCR) engagement, is important for this process. The disruption of NF-κB signaling in both mouse models and human cells impairs the localization of Xist RNA and alters the expression of certain X-linked genes. This disruption may have significant implications for understanding sex differences in immune responses and the development of autoimmune diseases.<br /> <br /> <b><span style="font-size:16px">Technologies and Advances</span></b><br /> In her ncRNA research, Anguera explained that her group uses a variety of techniques. The most beneficial has been RNA FISH (fluorescence in situ hybridization). Despite being an older method, RNA FISH was essential for identifying that Xist RNA is expressed but not properly localized on the inactive X chromosome in immune cells. Anguera noted that this discovery would likely be missed by more modern methods like RNA-seq and microarrays.<br /> <br /> One major technological advancement in ncRNA research has been the ability to directly sequence RNA. “Prior to nanopore sequencing, there was no way for scientists to directly analyze RNA molecules with sequencing technologies,” explained Libby Snell, Ph.D., Director of RNA and cDNA Sample Technology at Oxford Nanopore Technologies. “Instead, RNA had to be converted to cDNA, and the information gleaned from cDNA analysis was used to infer knowledge about the original RNA. That step adds cost and complexity, but more importantly, it can introduce errors and strip out useful information. Furthermore, the act of converting RNA to cDNA can suffer from certain biases due to the nature of the sequence within the RNA transcripts.”<br /> <br /> Snell highlighted recent improvements in their RNA analysis tools, specifically their newest RNA004 chemistry, which offers 98.8% single-read accuracy and can generate up to 20-30 million reads per sample. These developments have enhanced the detection of ncRNAs, particularly long non-coding RNAs (lncRNAs) that were previously undetectable. Snell also emphasized that the ability to study RNA directly, without converting it to cDNA, has opened up new possibilities for scientific research. This direct approach has led to the discovery of numerous novel lncRNAs, expanding the catalog of known ncRNAs. These discoveries are helping scientists uncover the functions of these molecules, with recent advances seen in fields like <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.35100" target="_blank">precision oncology</a>, <a href="https://www.mdpi.com/2073-4425/14/3/610" target="_blank">parasite biology</a>, and <a href="https://link.springer.com/article/10.1186/s12864-023-09552-6" target="_blank">extracellular vesicle analysis</a>. However, Snell acknowledged that one of the biggest challenges in ncRNA research is making sense of novel findings that deviate from what was previously inferred using cDNA-based analysis. Direct RNA sequencing is helping to address this by providing more comprehensive and accurate RNA data.<br /> <br /> “Next-generation sequencing has been a huge step forward in understanding the role of RNA in biology, and I believe with long-read, direct RNA sequencing, we are now taking the next big leap by empowering scientists with novel analysis possibilities, including nucleoside modifications within the context of full-length transcript information,” stated Snell. “The discoveries made today will become the foundation for understanding and interpreting non-coding RNAs in the decades ahead.”<br /> <br /> <b>References</b><ol class="decimal"><li>Shang R, Lee S, Senavirathne G, Lai EC. microRNAs in action: biogenesis, function and regulation. <i>Nature Reviews Genetics</i>. 2023;24(12):816-833. doi:<a href="https://doi.org/10.1038/s41576-023-00611-y" target="_blank">https://doi.org/10.1038/s41576-023-00611-y</a></li> <li>Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin4 encodes small RNAs with antisense complementarity to lin14. <i>Cell</i>. 1993;75(5):843-854. doi:<a href="https://doi.org/10.1016/0092-8674(93)90529-Y" target="_blank">https://doi.org/10.1016/0092-8674(93)90529-Y</a></li> <li>Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin14 by lin4 mediates temporal pattern formation in C. elegans. <i>Cell</i>. 1993;75(5):855-862. doi:<a href="https://doi.org/10.1016/0092-8674(93)90530-4" target="_blank">https://doi.org/10.1016/0092-8674(93)90530-4</a></li> <li>Wang J, Syrett CM, Kramer MC, Basu A, Atchison ML, Anguera, Montserrat C. Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. <i>Proceedings of the National Academy of Sciences</i>. 2016;113(14):E2029-E2038. doi:<a href="https://doi.org/10.1073/pnas.1520113113" target="_blank">https://doi.org/10.1073/pnas.1520113113</a></li> <li>Lovell CD, Jiwrajka N, Amerman HK, Cancro MP, Anguera, Montserrat C. <i>Xist</i> Deletion in B Cells Results in Systemic Lupus Erythematosus Phenotypes. <i>bioRxiv</i>. Published online January 1, 2024:2024.05.15.594175. doi:<a href="https://doi.org/10.1101/2024.05.15.594175" target="_blank">https://doi.org/10.1101/2024.05.15.594175</a></li> <li>Forsyth KS, Toothacre NE, Jiwrajka N, et al. NF-κB Signaling is Required for X-Chromosome Inactivation Maintenance Following T cell Activation. <i>bioRxiv</i>. Published online January 1, 2024:2024.02.08.579505. doi:<a href="https://doi.org/10.1101/2024.02.08.579505" target="_blank">https://doi.org/10.1101/2024.02.08.579505</a></li> </ol><br /> </div> </div> <div class="b-post__footer h-hide--on-preview h-clear h-padding-bottom-m h-margin-horiz-xl"> <div class="h-clearfix"> <div class="h-margin-bottom-xl h-margin-top-none h-text-size--11" id="content-tags-326160"> <strong>Tags:</strong> <span class="js-content-tag-none">None</span> </div> <hr class="b-divider b-divider--post-controls" /> <ul class="h-left js-post-info"> </ul> <ul class="h-margin-top-s h-right js-post-controls b-comp-menu-horizontal js-comp-menu-horizontal js-comp-menu--dropdown-on-xsmall b-comp-menu-dropdown--inactive" data-node-id="326160" data-dropdown-icon-classes="b-icon b-icon__ellipsis" data-dropdown-content-classes="b-comp-menu-dropdown__content--right"> <li id="vote-326160" class="h-margin-top-xs b-post-control b-post-control--responsive b-post-control__bubble-flyout-container b-post-control--disabled js-comp-menu--exclude-from-dropdown " tabindex="0"> <span class="b-icon b-icon__like b-post-control__icon"></span><span class="b-post-control__label">Likes</span> <span class="bubble-flyout b-post-control__bubble-flyout"> <i></i> <u></u> <span class="bubble-content votecount ">1</span> </span> </li> </ul> </div> </div> <div class="edit-conversation-container OLD__edit-conversation-container"></div> <div class="b-comments js-comments b-comments--article js-comments--article h-margin-bottom-xl h-clearfix h-hide"> <div class="b-comments__header js-comments__header b-media h-padding-vert-m h-padding-horiz-l h-hide"> <div class="js-comments__total h-margin-left-l b-media__body"> <span class="b-icon b-icon__speech-single h-margin-right-s"></span> <label class="js-comments__total-text h-align-top"></label> </div> <div class="b-media__img--rev js-comments__pagination h-hide"> <label></label> <span class="b-comments__pagination--up js-comments__page--prev h-margin-left-s" title="See previous comments"><span class="b-icon b-icon__arrow-up-m"></span></span> </div> </div> <ul class="b-comments__comments js-comments__comments h-left"></ul> <div class="b-comments__footer js-comments__footer b-media h-padding-vert-m h-padding-horiz-l h-clear h-hide"> <div class="b-media__img--rev js-comments__pagination"> <label></label> <span class="b-comments__pagination--down js-comments__page--next h-margin-left-s" title="See next comments"><span class="b-icon b-icon__arrow-down-m"></span></span> </div> </div> </div> <div class="notice comment-disabled"> Please sign into your account to post comments. </div> </div> </div> </li> </ul> </div> </div> </div> </div> <script type="text/javascript"> (function(){ window.vBulletin = window.vBulletin || {}; vBulletin.widget = vBulletin.widget || {}; vBulletin.conversation = vBulletin.conversation || {}; vBulletin.conversation.COMMENTS_PER_PAGE = Number('25') || 25; vBulletin.conversation.POSTS_PER_PAGE = Number('') || 15; })(); </script>   <div class="b-module canvas-widget default-widget custom-html-widget" id="widget_224" data-widget-id="64" data-widget-instance-id="224"> <div class="widget-header h-clearfix"> <div class="module-title h-left"> <h1 class="main-title js-main-title hide-on-editmode">About the Author</h1> </div> <div class="module-buttons"> <span class="toggle-button module-button-item collapse" title="Collapse" data-toggle-title="Expand"><span class="b-icon b-icon__toggle-collapse">Collapse</span></span> </div> </div> <hr class="widget-header-divider" /> <div class="widget-content"> <a href="https://www.seqanswers.com/member/146502-seqadmin" class="avatar medium h-left"> <img src="./core/image.php?userid=146502&thumb=1&dateline=1673964993" alt="seqadmin" title="seqadmin" /> </a> Benjamin Atha holds a B.A. in biology from Hood College and an M.S. in biological sciences from Towson University. With over 9 years of hands-on laboratory experience, he's well-versed in next-generation sequencing systems. Ben is currently the editor for SEQanswers. 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This approach offers personalized treatment and wellness plans by utilizing insights from each person's unique biology and lifestyle to deliver more effective care. Its advancement relies on innovative technologies that enable a deeper understanding of individual variability. In a joint documentary with our colleagues at Biocompare, we examined the foundational principles of precision... </div> <div class="list-item-footer h-clearfix"> <ul class="replylike_count h-left"> <li id="channel-326391"> <div class="channel h-left"> <div class="channel_text"> Channel: <a href="https://www.seqanswers.com/articles">Articles</a> </div> </div> </li> </ul> </div> <div class="b-post-sm__date">01-27-2025, 07:46 AM</div> </div> </li> <li class="b-post-sm js-post-sm" data-nodeid="326349"> <div class="b-post-sm__content"> <div class="b-post-sm__title ellipsis"> <a href="https://www.seqanswers.com/articles/326349-recent-innovations-in-spatial-biology">Recent Innovations in Spatial Biology</a> </div> <div class="b-post-sm__author"> by <a href="https://www.seqanswers.com/member/146502-seqadmin" data-vbnamecard="146502">seqadmin</a> </div> <div class="b-post-sm__post-content post-content ellipsis restore"> <br /> <br /> Spatial biology is an exciting field that encompasses a wide range of techniques and technologies aimed at mapping the organization and interactions of various biomolecules in their native environments. As this area of research progresses, new tools and methodologies are being introduced, accompanied by efforts to establish benchmarking standards and drive technological innovation.<br /> <br /> <span style="font-size:16px"><b>3D Genomics</b></span><br /> While spatial biology often involves studying proteins and RNAs in their... </div> <div class="list-item-footer h-clearfix"> <ul class="replylike_count h-left"> <li id="channel-326349"> <div class="channel h-left"> <div class="channel_text"> Channel: <a href="https://www.seqanswers.com/articles">Articles</a> </div> </div> </li> </ul> </div> <div class="b-post-sm__date">01-01-2025, 07:30 PM</div> </div> </li> </ul> <div class="widget-footer h-align-left h-clear"> <a href="https://www.seqanswers.com/search?r=89191193" class="b-button">View All</a> </div> </div> </div>   <div class="b-module js-module canvas-widget default-widget axd-widget axd-container" id="widget_213" data-widget-id="45" data-widget-instance-id="213"> <div class="widget-header h-clearfix"> <div class="module-title h-left"> <h1 class="main-title js-main-title hide-on-editmode">ad_right_rmr</h1> </div> <div class="module-buttons"> <span class="toggle-button module-button-item collapse" title="Collapse" data-toggle-title="Expand"><span class="b-icon b-icon__toggle-collapse">Collapse</span></span> </div> </div> <div class="widget-content restore axd axd_213"> <div class="axd-inner js-module__hide-if-empty "> <div class="ad_213_inner"> <span id=zone803333780></span> <script> (function(r,d,u) { var s = d.createElement(r); s.async = true; u += '&cb=' + Date.now() + Math.random(); s.src = u; var n = d.getElementsByTagName(r)[0]; n.parentNode.insertBefore(s, n); })('script',document,'//comparenetworks.engine.adglare.net/?803333780'); </script></div> </div> </div> </div>   <div class="b-module canvas-widget search-widget" id="widget_207" data-widget-id="12" data-widget-instance-id="207"> <div class="widget-header h-clearfix"> <div class="module-title h-left"> <h1 class="main-title js-main-title hide-on-editmode">News</h1> </div> <div class="module-buttons"> <span class="toggle-button module-button-item collapse" title="Collapse" data-toggle-title="Expand"><span class="b-icon b-icon__toggle-collapse">Collapse</span></span> </div> </div> <hr class="widget-header-divider" /> <div class="widget-content"> <ul class="conversation-list list-container h-clearfix"> <li class="b-post-sm js-post-sm" data-nodeid="326412"> <div class="b-post-sm__avatar avatar h-left"> <a href="https://www.seqanswers.com/member/146502-seqadmin"> <img src="./core/image.php?userid=146502&thumb=1&dateline=1673964993" width="32" height="32" alt="seqadmin" /> </a> </div> <div class="b-post-sm__content b-post-sm__content--has-avatar"> <div class="b-post-sm__title ellipsis"> <a href="https://www.seqanswers.com/forum/news/326412-genetic-mapping-of-plasmodium-knowlesi-identifies-essential-genes-and-drug-resistance-mechanisms">Genetic Mapping of Plasmodium knowlesi Identifies Essential Genes and Drug Resistance Mechanisms</a> </div> <div class="b-post-sm__author"> by <a href="https://www.seqanswers.com/member/146502-seqadmin" data-vbnamecard="146502">seqadmin</a> </div> <div class="b-post-sm__post-content post-content ellipsis restore"> Researchers at Harvard T.H. Chan School of Public Health and their collaborators created a comprehensive map of genes needed for blood infections from... </div> <div class="list-item-footer h-clearfix"> <ul class="replylike_count h-left"> <li id="channel-326412"> <div class="channel h-left"> <div class="channel_text"> Channel: <a href="https://www.seqanswers.com/forum/news">News</a> </div> </div> </li> </ul> </div> <div class="b-post-sm__date">02-07-2025, 09:30 AM</div> </div> </li> <li class="b-post-sm js-post-sm" data-nodeid="326410"> <div class="b-post-sm__avatar avatar h-left"> <a href="https://www.seqanswers.com/member/146502-seqadmin"> <img src="./core/image.php?userid=146502&thumb=1&dateline=1673964993" width="32" height="32" alt="seqadmin" /> </a> </div> <div class="b-post-sm__content b-post-sm__content--has-avatar"> <div class="b-post-sm__title ellipsis"> <a href="https://www.seqanswers.com/forum/news/326410-new-dna-sequencing-method-measures-metabolites-with-high-precision">New DNA Sequencing Method Measures Metabolites with High Precision</a> </div> <div class="b-post-sm__author"> by <a href="https://www.seqanswers.com/member/146502-seqadmin" data-vbnamecard="146502">seqadmin</a> </div> <div class="b-post-sm__post-content post-content ellipsis restore"> Scientists from the University of Toronto have developed a new technique for small molecule sequencing named, “smol-seq.” This platform uses DNA sequencing... </div> <div class="list-item-footer h-clearfix"> <ul class="replylike_count h-left"> <li id="channel-326410"> <div class="channel h-left"> <div class="channel_text"> Channel: <a href="https://www.seqanswers.com/forum/news">News</a> </div> </div> </li> </ul> </div> <div class="b-post-sm__date">02-05-2025, 10:34 AM</div> </div> </li> <li class="b-post-sm js-post-sm" data-nodeid="326405"> <div class="b-post-sm__avatar avatar h-left"> <a href="https://www.seqanswers.com/member/146502-seqadmin"> <img src="./core/image.php?userid=146502&thumb=1&dateline=1673964993" width="32" height="32" alt="seqadmin" /> </a> </div> <div class="b-post-sm__content b-post-sm__content--has-avatar"> <div class="b-post-sm__title ellipsis"> <a href="https://www.seqanswers.com/forum/news/326405-ai-model-maps-3d-genome-structures-in-minutes">AI Model Maps 3D Genome Structures in Minutes</a> </div> <div class="b-post-sm__author"> by <a href="https://www.seqanswers.com/member/146502-seqadmin" data-vbnamecard="146502">seqadmin</a> </div> <div class="b-post-sm__post-content post-content ellipsis restore"> <b>A Faster, AI-Powered Approach to Chromatin Structure Prediction</b><br /> The three-dimensional organization of DNA within the nucleus plays a fundamental... </div> <div class="list-item-footer h-clearfix"> <ul class="replylike_count h-left"> <li id="channel-326405"> <div class="channel h-left"> <div class="channel_text"> Channel: <a href="https://www.seqanswers.com/forum/news">News</a> </div> </div> </li> </ul> </div> <div class="b-post-sm__date">02-03-2025, 09:07 AM</div> </div> </li> <li class="b-post-sm js-post-sm" data-nodeid="326400"> <div class="b-post-sm__avatar avatar h-left"> <a href="https://www.seqanswers.com/member/146502-seqadmin"> <img src="./core/image.php?userid=146502&thumb=1&dateline=1673964993" width="32" height="32" alt="seqadmin" /> </a> </div> <div class="b-post-sm__content b-post-sm__content--has-avatar"> <div class="b-post-sm__title ellipsis"> <a href="https://www.seqanswers.com/forum/news/326400-long-read-sequencing-speeds-up-diagnosis-of-rare-genetic-diseases">Long-Read Sequencing Speeds Up Diagnosis of Rare Genetic Diseases</a> </div> <div class="b-post-sm__author"> by <a href="https://www.seqanswers.com/member/146502-seqadmin" data-vbnamecard="146502">seqadmin</a> </div> <div class="b-post-sm__post-content post-content ellipsis restore"> <br /> <br /> <br /> <br /> Despite advances in genetic testing, half of all rare genetic diseases remain undiagnosed. 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