{"id":46172,"date":"2022-01-18T10:00:00","date_gmt":"2022-01-18T09:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=46172"},"modified":"2024-03-22T15:24:43","modified_gmt":"2024-03-22T14:24:43","slug":"capturing-snapshots-of-a-crucial-step-in-rna-splicing","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/capturing-snapshots-of-a-crucial-step-in-rna-splicing\/","title":{"rendered":"Capturing &#8216;snapshots&#8217; of a crucial step in RNA splicing"},"content":{"rendered":"\n<p>The Galej group at EMBL Grenoble has recently obtained high resolution snapshots of the dynamic rearrangements of the U2 snRNP complex, a crucial component of the human spliceosome. This macromolecular complex is responsible for sorting out coding from non-coding segments during RNA splicing \u2013 the process by which information in messenger RNAs is rearranged, allowing them to produce functional proteins. These results have been <a href=\"https:\/\/europepmc.org\/article\/MED\/34822310\" target=\"_blank\" rel=\"noreferrer noopener\">published in <em>Science<\/em><\/a>.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Sorting out the right information<\/strong><\/h2>\n\n\n\n<p><em>DNA makes RNA makes protein.<\/em> This seemingly simple phrase, describing how genes are transcribed into messenger RNAs and subsequently translated into proteins, hides a multitude of intricate molecular steps. In eukaryotes \u2013 organisms like animals, plants and fungi \u2013 one of these steps is called RNA splicing.&nbsp;<\/p>\n\n\n\n<p>Splicing is necessary because nearly all genes in eukaryotic cells include segments called introns, which are not required to make a protein. In order to create proteins that function properly, the cell needs to remove introns from the mRNA molecule, retaining only exons &#8211; the segments that carry protein-coding information. This reaction is catalysed by a large macromolecular complex called the \u2018spliceosome\u2019.<\/p>\n\n\n\n<p>Spliceosomes are complex and highly dynamic molecular machines, which makes them very difficult to study with traditional structural biology methods. Now, cryo-electron microscopy (cryo-EM) techniques have allowed researchers in the Galej group at EMBL Grenoble to show how the spliceosome recognises the branch site, a key position within introns which influences the outcome of the splicing reaction.<\/p>\n\n\n\n<p>Branch sites are located close to the ends of introns. Because of this location, they are important for determining where an intron ends and the protein-coding sequence begins again. This means that without them, a messenger RNA that describes a fully functional protein cannot be produced.<\/p>\n\n\n\n<p>The researchers used cryo-EM to obtain snapshots of the molecular structure of the U2 snRNP complex, the component of the spliceosome that recognises the branch site. \u201cWe developed a novel method to purify these complex particles directly from human cells and determined their 3D structure at a very high resolution,\u201d said Jonas Tholen, first author of the paper and PhD student in the Galej group. \u201cAtomic details allow us to see precisely how different proteins and RNAs interact with each other and with the branch site.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>A crucial step in gene expression<\/strong><\/h2>\n\n\n\n<p>Combining these structures with biochemical assays, the scientists were able to describe in detail the mechanism by which the spliceosome recognises branch sites and executes the splicing process at precisely these locations.<\/p>\n\n\n\n<p>They could find two previously unknown intermediates of the complex during the splicing process and show that an additional protein \u2013 SF3B6 \u2013 plays an important role in stabilising the branch site within the spliceosome. \u201cA series of biochemical studies from 25 years ago indicated that this protein is very important for the splicing reaction, but its precise function remained elusive. With our new insights, we could explain those early observations,\u201d explained Wojciech Galej.<\/p>\n\n\n\n<p>\u201cSome estimates predict that up to 60% of genetic disorders occur in relation to problems with splicing signals or malfunctions of the splicing machinery,\u201d added Galej. \u201cThis makes the splicing machinery a potential drug target for treating some genetic diseases. Understanding the molecular and atomic details of the splicing mechanism opens up new possibilities for identifying or developing drugs that can modulate this process in treating certain genetic diseases.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The Galej group at EMBL Grenoble has recently obtained high resolution snapshots of a crucial step in RNA splicing involving the U2 snRNP complex, a crucial component of the human spliceosome.<\/p>\n","protected":false},"author":106,"featured_media":46184,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[718,485,183,37,3628,35],"embl_taxonomy":[9792,19261,5148],"class_list":["post-46172","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-cryo-em","tag-galej","tag-gene-expression","tag-grenoble","tag-splicing","tag-structural-biology","embl_taxonomy-embl-grenoble","embl_taxonomy-galej-group","embl_taxonomy-structural-biology-embl-grenoble"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","article_intro":"<p>Cryo-electron microscopy sheds light on RNA splicing<\/p>\n","related_links":[{"link_description":"Galej group","link_url":"https:\/\/www.embl.org\/groups\/galej\/"},{"link_description":"At the core of the Integrator complex","link_url":"https:\/\/www.embl.org\/news\/science\/at-the-core-of-the-integrator-complex\/"},{"link_description":"EMBL scientists receive prestigious ERC starting grants","link_url":"https:\/\/www.embl.org\/news\/lab-matters\/erc-grants-2020\/"}],"source_article":[{"publication_title":"Structural basis of branch site recognition by the human spliceosome.","publication_link":{"title":"","url":"https:\/\/www.science.org\/doi\/10.1126\/science.abm4245","target":"_blank"},"publication_authors":"Tholen J., et al.","publication_source":"Science","publication_date":"25 November 2021","publication_doi":"10.1126\/science.abm4245"}],"in_this_article":false,"press_contact":"None","vf_locked":false,"field_article_language":{"value":"english","label":"English"},"article_translations":false,"languages":""},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"b14d3f13-5670-44fb-8970-e54dfd9c921a\";i:1;s:36:\"89e00fee-87f4-482e-a801-4c3548bb6a58\";i:2;s:36:\"8f81131e-d37c-470c-848f-618fce652295\";}","parents":[],"name":["EMBL Grenoble"],"slug":"embl-grenoble","description":"Where &gt; All EMBL sites &gt; EMBL Grenoble"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"fc528877-4017-438f-85b4-de2b54c443f1\";i:2;s:36:\"b3d9805e-9765-4a93-a6bb-56dfdc7142ff\";}","parents":[],"name":["Galej Group"],"slug":"galej-group","description":"What &gt; Structural Biology (EMBL Grenoble) &gt; Galej Group"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"7ca3ce91-dc32-47ea-8d4b-7a53c3a3a9fd\";i:2;s:36:\"fc528877-4017-438f-85b4-de2b54c443f1\";}","parents":[],"name":["Structural Biology (EMBL Grenoble)"],"slug":"structural-biology-embl-grenoble","description":"What &gt; Research Units &gt; Structural Biology (EMBL Grenoble)"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Capturing &#039;snapshots&#039; of a crucial step in RNA splicing | EMBL<\/title>\n<meta name=\"description\" content=\"The Galej group at EMBL Grenoble has recently obtained high resolution snapshots of a crucial step in RNA splicing involving the U2 snRNP complex, a crucial component of the human spliceosome.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/capturing-snapshots-of-a-crucial-step-in-rna-splicing\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Capturing &#039;snapshots&#039; 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