{"id":1170,"date":"2021-11-27T10:36:13","date_gmt":"2021-11-27T10:36:13","guid":{"rendered":"https:\/\/www.embl.org\/groups\/galej\/?p=1170"},"modified":"2021-11-27T10:36:13","modified_gmt":"2021-11-27T10:36:13","slug":"structure-of-the-human-u2-snrnp","status":"publish","type":"post","link":"https:\/\/www.embl.org\/groups\/galej\/blog\/2021\/11\/structure-of-the-human-u2-snrnp\/","title":{"rendered":"Structure of the human U2 snRNP"},"content":{"rendered":"\n<p>Our new paper on the structure of the human U2 snRNP was just published in Science !<\/p>\n\n\n\n<p>In human cells protein-coding genetic information is punctuated with non-coding segments &#8211; Introns, which need to be removed from pre-mRNA by the spliceosome. U2 snRNP recognises a conserved position within the intron, so called branch site. <\/p>\n\n\n\n<p><strong>Jonas Tholen<\/strong>, PhD student in our group, established a new CRISPR\/Cas9-based method to specifically purify U2 snRNP complexes directly from human cells and reconstituted <em>in vitro <\/em>branch site recognition reaction. We identified <strong>two novel splicing complexes<\/strong> and determined a series of structures providing snapshots of the intron recognition process. cryo-EM reconstructions were determined at <strong>close to 2.0 \u00c5 resolution<\/strong> in the best parts, first time for any splicing complex.<br>Our data revealed how a small protein &#8211; <strong>SF3B6 stabilises branch helix<\/strong>. This has important implications for introns recognition in species which dont have strong branch-site signals (i.e. humans). SF3B6 enforces helical geometry of the U2 snRNA and may facilitate binding of pre-mRNAs without perfect sequence complementarity. ATP-dependent remodelling decoupled from the pre-mRNA binding revealed a new conformation of the U2 snRNA, which competes directly with the pre-mRNA substrate and provided <strong>a mechanism for the branch site stability selection.<\/strong><\/p>\n\n\n\n<figure class=\"vf-figure wp-block-image size-large\"><a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.abm4245\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"697\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/groups\/galej\/wp-content\/uploads\/2021\/11\/Science-1024x697.png\" alt=\"\" class=\"wp-image-1172\" srcset=\"https:\/\/www.embl.org\/groups\/galej\/wp-content\/uploads\/2021\/11\/Science-1024x697.png 1024w, https:\/\/www.embl.org\/groups\/galej\/wp-content\/uploads\/2021\/11\/Science-300x204.png 300w, https:\/\/www.embl.org\/groups\/galej\/wp-content\/uploads\/2021\/11\/Science-768x523.png 768w, https:\/\/www.embl.org\/groups\/galej\/wp-content\/uploads\/2021\/11\/Science-1536x1045.png 1536w, https:\/\/www.embl.org\/groups\/galej\/wp-content\/uploads\/2021\/11\/Science.png 1802w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a><\/figure>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Our new paper on the structure of the human U2 snRNP was just published in Science ! In human cells protein-coding genetic information is punctuated with non-coding segments &#8211; Introns, which need to be removed from pre-mRNA by the spliceosome. U2 snRNP recognises a conserved position within&hellip;<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2029],"tags":[],"embl_taxonomy":[],"class_list":["post-1170","post","type-post","status-publish","format-standard","hentry","category-science"],"acf":[],"embl_taxonomy_terms":[],"featured_image_src":"https:\/\/www.embl.org\/groups\/galej\/wp-includes\/images\/media\/default.svg","_links":{"self":[{"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/posts\/1170","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/comments?post=1170"}],"version-history":[{"count":1,"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/posts\/1170\/revisions"}],"predecessor-version":[{"id":1174,"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/posts\/1170\/revisions\/1174"}],"wp:attachment":[{"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/media?parent=1170"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/categories?post=1170"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/tags?post=1170"},{"taxonomy":"embl_taxonomy","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/galej\/wp-json\/wp\/v2\/embl_taxonomy?post=1170"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}