Structure of a transcribing RNA polymerase II-U1 snRNP complex
To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo-electron microscopy structure of a mammalian transcribing Pol II-U1 snRNP complex. The struct...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2021-01, Vol.371 (6526), p.305-309 |
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| creator | Zhang, Suyang Aibara, Shintaro Vos, Seychelle M Agafonov, Dmitry E Lührmann, Reinhard Cramer, Patrick |
| description | To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo-electron microscopy structure of a mammalian transcribing Pol II-U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5' splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to the formation of a "growing intron loop." Loop formation may facilitate scanning of nascent pre-mRNA for the 3' splice site, functional pairing of distant intron ends, and prespliceosome assembly. Our results provide a starting point for a mechanistic analysis of cotranscriptional spliceosome assembly and the biogenesis of mRNA isoforms by alternative splicing. |
| doi_str_mv | 10.1126/science.abf1870 |
| format | Article |
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Here, we report the cryo-electron microscopy structure of a mammalian transcribing Pol II-U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5' splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to the formation of a "growing intron loop." Loop formation may facilitate scanning of nascent pre-mRNA for the 3' splice site, functional pairing of distant intron ends, and prespliceosome assembly. Our results provide a starting point for a mechanistic analysis of cotranscriptional spliceosome assembly and the biogenesis of mRNA isoforms by alternative splicing.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.abf1870</identifier><identifier>PMID: 33446560</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Alternative Splicing ; Animals ; Assembly ; Cryoelectron Microscopy ; Deoxyribonucleic acid ; DNA ; DNA-directed RNA polymerase ; Electron microscopy ; Eukaryotes ; Gene expression ; Humans ; Introns ; Isoforms ; Microscopy ; Molecular structure ; Nucleic Acid Conformation ; Protein Binding ; Protein Domains ; Ribonucleic acid ; Ribonucleoprotein, U1 Small Nuclear - chemistry ; Ribonucleoproteins (small nuclear) ; RNA ; RNA polymerase ; RNA polymerase II ; RNA Polymerase II - chemistry ; RNA Precursors - chemistry ; RNA, Messenger - biosynthesis ; RNA, Messenger - chemistry ; Spliceosomes - chemistry ; Spliceosomes - metabolism ; Splicing ; Sus scrofa ; Transcription ; Transcription, Genetic</subject><ispartof>Science (American Association for the Advancement of Science), 2021-01, Vol.371 (6526), p.305-309</ispartof><rights>Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</rights><rights>Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-2d7adf5c8f2b3bc4fa4aeb563f723d10158ab36e216890fbf6853eb0c7f840893</citedby><cites>FETCH-LOGICAL-c432t-2d7adf5c8f2b3bc4fa4aeb563f723d10158ab36e216890fbf6853eb0c7f840893</cites><orcidid>0000-0003-2221-482X ; 0000-0002-4438-4099 ; 0000-0001-5454-7755 ; 0000-0003-1985-2994 ; 0000-0002-2322-9276</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2884,2885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33446560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Suyang</creatorcontrib><creatorcontrib>Aibara, Shintaro</creatorcontrib><creatorcontrib>Vos, Seychelle M</creatorcontrib><creatorcontrib>Agafonov, Dmitry E</creatorcontrib><creatorcontrib>Lührmann, Reinhard</creatorcontrib><creatorcontrib>Cramer, Patrick</creatorcontrib><title>Structure of a transcribing RNA polymerase II-U1 snRNP complex</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo-electron microscopy structure of a mammalian transcribing Pol II-U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5' splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to the formation of a "growing intron loop." Loop formation may facilitate scanning of nascent pre-mRNA for the 3' splice site, functional pairing of distant intron ends, and prespliceosome assembly. Our results provide a starting point for a mechanistic analysis of cotranscriptional spliceosome assembly and the biogenesis of mRNA isoforms by alternative splicing.</description><subject>Alternative Splicing</subject><subject>Animals</subject><subject>Assembly</subject><subject>Cryoelectron Microscopy</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA-directed RNA polymerase</subject><subject>Electron microscopy</subject><subject>Eukaryotes</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Introns</subject><subject>Isoforms</subject><subject>Microscopy</subject><subject>Molecular structure</subject><subject>Nucleic Acid Conformation</subject><subject>Protein Binding</subject><subject>Protein Domains</subject><subject>Ribonucleic acid</subject><subject>Ribonucleoprotein, U1 Small Nuclear - chemistry</subject><subject>Ribonucleoproteins (small nuclear)</subject><subject>RNA</subject><subject>RNA polymerase</subject><subject>RNA polymerase II</subject><subject>RNA Polymerase II - chemistry</subject><subject>RNA Precursors - chemistry</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - chemistry</subject><subject>Spliceosomes - chemistry</subject><subject>Spliceosomes - metabolism</subject><subject>Splicing</subject><subject>Sus scrofa</subject><subject>Transcription</subject><subject>Transcription, Genetic</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkM1LwzAYxoMobk7P3iTgxUu3N0mTphdhDD8GMmW6c0nSRDr6MZMW3H9vddWDp-fw_t6Hhx9ClwSmhFAxC6awtbFTpR2RCRyhMYGURykFdozGAExEEhI-QmchbAH6W8pO0YixOBZcwBjdvra-M23nLW4cVrj1qg7GF7qo3_F6Nce7ptxX1qtg8XIZbQgO9Xr1gk1T7Ur7eY5OnCqDvRhygjb3d2-Lx-jp-WG5mD9FJma0jWieqNxxIx3VTJvYqVhZzQVzCWU5AcKl0kxYSoRMwWknJGdWg0mcjEGmbIJuDr0733x0NrRZVQRjy1LVtulCRuNE8lRIlvTo9T9023S-7tf9UJAyIklPzQ6U8U0I3rps54tK-X1GIPtWmw1qs0Ft_3E19Ha6svkf_-uSfQFhynTy</recordid><startdate>20210115</startdate><enddate>20210115</enddate><creator>Zhang, Suyang</creator><creator>Aibara, Shintaro</creator><creator>Vos, Seychelle M</creator><creator>Agafonov, Dmitry E</creator><creator>Lührmann, Reinhard</creator><creator>Cramer, Patrick</creator><general>The American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2221-482X</orcidid><orcidid>https://orcid.org/0000-0002-4438-4099</orcidid><orcidid>https://orcid.org/0000-0001-5454-7755</orcidid><orcidid>https://orcid.org/0000-0003-1985-2994</orcidid><orcidid>https://orcid.org/0000-0002-2322-9276</orcidid></search><sort><creationdate>20210115</creationdate><title>Structure of a transcribing RNA polymerase II-U1 snRNP complex</title><author>Zhang, Suyang ; Aibara, Shintaro ; Vos, Seychelle M ; Agafonov, Dmitry E ; Lührmann, Reinhard ; Cramer, Patrick</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-2d7adf5c8f2b3bc4fa4aeb563f723d10158ab36e216890fbf6853eb0c7f840893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alternative Splicing</topic><topic>Animals</topic><topic>Assembly</topic><topic>Cryoelectron Microscopy</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA-directed RNA polymerase</topic><topic>Electron microscopy</topic><topic>Eukaryotes</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Introns</topic><topic>Isoforms</topic><topic>Microscopy</topic><topic>Molecular structure</topic><topic>Nucleic Acid Conformation</topic><topic>Protein Binding</topic><topic>Protein Domains</topic><topic>Ribonucleic acid</topic><topic>Ribonucleoprotein, U1 Small Nuclear - chemistry</topic><topic>Ribonucleoproteins (small nuclear)</topic><topic>RNA</topic><topic>RNA polymerase</topic><topic>RNA polymerase II</topic><topic>RNA Polymerase II - chemistry</topic><topic>RNA Precursors - chemistry</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - chemistry</topic><topic>Spliceosomes - chemistry</topic><topic>Spliceosomes - metabolism</topic><topic>Splicing</topic><topic>Sus scrofa</topic><topic>Transcription</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Suyang</creatorcontrib><creatorcontrib>Aibara, Shintaro</creatorcontrib><creatorcontrib>Vos, Seychelle M</creatorcontrib><creatorcontrib>Agafonov, Dmitry E</creatorcontrib><creatorcontrib>Lührmann, Reinhard</creatorcontrib><creatorcontrib>Cramer, Patrick</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Suyang</au><au>Aibara, Shintaro</au><au>Vos, Seychelle M</au><au>Agafonov, Dmitry E</au><au>Lührmann, Reinhard</au><au>Cramer, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure of a transcribing RNA polymerase II-U1 snRNP complex</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2021-01-15</date><risdate>2021</risdate><volume>371</volume><issue>6526</issue><spage>305</spage><epage>309</epage><pages>305-309</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><abstract>To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo-electron microscopy structure of a mammalian transcribing Pol II-U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5' splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to the formation of a "growing intron loop." Loop formation may facilitate scanning of nascent pre-mRNA for the 3' splice site, functional pairing of distant intron ends, and prespliceosome assembly. 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| subjects | Alternative Splicing Animals Assembly Cryoelectron Microscopy Deoxyribonucleic acid DNA DNA-directed RNA polymerase Electron microscopy Eukaryotes Gene expression Humans Introns Isoforms Microscopy Molecular structure Nucleic Acid Conformation Protein Binding Protein Domains Ribonucleic acid Ribonucleoprotein, U1 Small Nuclear - chemistry Ribonucleoproteins (small nuclear) RNA RNA polymerase RNA polymerase II RNA Polymerase II - chemistry RNA Precursors - chemistry RNA, Messenger - biosynthesis RNA, Messenger - chemistry Spliceosomes - chemistry Spliceosomes - metabolism Splicing Sus scrofa Transcription Transcription, Genetic |
| title | Structure of a transcribing RNA polymerase II-U1 snRNP complex |
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