{"id":6,"date":"2022-09-08T15:27:15","date_gmt":"2022-09-08T14:27:15","guid":{"rendered":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/?page_id=6"},"modified":"2022-09-13T12:16:38","modified_gmt":"2022-09-13T11:16:38","slug":"research","status":"publish","type":"page","link":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/research\/","title":{"rendered":"Research"},"content":{"rendered":"\n<p>Splicing of precursor messenger RNA (pre-mRNA) is a ubiquitous hallmark of gene expression in all eukaryotes. Within the cell, splicing occurs simultaneously with pre-mRNA synthesis by RNA polymerase II (Pol II) and is mechanistically coupled to transcription. The choice of the splice sites is not always unique, as a single gene can give rise to multiple functionally distinct mRNA isoforms through alternative splicing. In fact, more than 95% of human genes are alternatively spliced, massively expanding the coding potential of our genome. Dysregulation of alternative splicing contributes to cancer pathogenesis and is under study as a biomarker of diseases. Our research aims to understand the mechanism governing alternative splice site selection and the crosstalk between the transcription and splicing machineries.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large is-resized\" id=\"attachment_21113\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure1-1024x636.png\" alt=\"\" class=\"wp-image-62\" width=\"847\" height=\"526\" srcset=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure1-1024x636.png 1024w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure1-300x186.png 300w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure1-768x477.png 768w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure1-1536x954.png 1536w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure1-2048x1272.png 2048w\" sizes=\"auto, (max-width: 847px) 100vw, 847px\" \/><figcaption>Regulation of alternative splicing is coupled with transcription<\/figcaption><\/figure>\n<\/div>\n\n\n<p>We recently determined the cryo-EM structure of the transcribing Pol II in complex with U1 snRNP, the first spliceosomal building block that engages pre-mRNA. The structure revealed for the first time a direct protein interaction between the transcription and splicing machineries within a large supercomplex and provided insights into how functional pairing of distant intron ends and spliceosome assembly can occur on the Pol II surface.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\" id=\"attachment_21114\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure2.png\" alt=\"\" class=\"wp-image-63\" width=\"610\" height=\"430\" srcset=\"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure2.png 2438w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure2-300x211.png 300w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure2-1024x722.png 1024w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure2-768x541.png 768w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure2-1536x1082.png 1536w, https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-content\/uploads\/sites\/34\/Figure2-2048x1443.png 2048w\" sizes=\"auto, (max-width: 610px) 100vw, 610px\" \/><figcaption>Cryo-EM structure of the transcribing Pol II-U1 snRNP complex<\/figcaption><\/figure>\n<\/div>\n\n\n<p>Our lab employs a multidisciplinary approach combining biochemical reconstitution, functional assays, structural biology and&nbsp;<em>in vivo<\/em>&nbsp;RNA sequencing to define the molecular basis of transcription-coupled alternative splicing. Our long-term research goal is to understand how the transcription and splicing machineries functionally interact to regulate gene expression.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Splicing of precursor messenger RNA (pre-mRNA) is a ubiquitous hallmark of gene expression in all eukaryotes. Within the cell, splicing occurs simultaneously with pre-mRNA synthesis by RNA polymerase II (Pol II) and is mechanistically coupled to transcription. The choice of the splice sites is not always unique, as a single gene can give rise to [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"categories":[],"class_list":{"0":"post-6","1":"page","2":"type-page","3":"status-publish","5":"entry"},"featured_image_src":null,"featured_image_src_square":null,"_links":{"self":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/pages\/6","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/comments?post=6"}],"version-history":[{"count":9,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/pages\/6\/revisions"}],"predecessor-version":[{"id":154,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/pages\/6\/revisions\/154"}],"wp:attachment":[{"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/media?parent=6"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www2.mrc-lmb.cam.ac.uk\/groups\/zhang\/wp-json\/wp\/v2\/categories?post=6"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}