Molecular architecture of the human 17S U2 snRNP
The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing 1 . Stable addition of U2 during early spliceosome formation requires the DEAD-box ATPase PRP5 2 – 7 . Yeast U2 small nucl...
Gespeichert in:
Veröffentlicht in: | Nature (London) 2020-07, Vol.583 (7815), p.310-313 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 313 |
---|---|
container_issue | 7815 |
container_start_page | 310 |
container_title | Nature (London) |
container_volume | 583 |
creator | Zhang, Zhenwei Will, Cindy L. Bertram, Karl Dybkov, Olexandr Hartmuth, Klaus Agafonov, Dmitry E. Hofele, Romina Urlaub, Henning Kastner, Berthold Lührmann, Reinhard Stark, Holger |
description | The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing
1
. Stable addition of U2 during early spliceosome formation requires the DEAD-box ATPase PRP5
2
–
7
. Yeast U2 small nuclear RNA (snRNA) nucleotides that form base pairs with the branch site are initially sequestered in a branchpoint-interacting stem–loop (BSL)
8
, but whether the human U2 snRNA folds in a similar manner is unknown. The U2 SF3B1 protein, a common mutational target in haematopoietic cancers
9
, contains a HEAT domain (SF3B1
HEAT
) with an open conformation in isolated SF3b
10
, but a closed conformation in spliceosomes
11
, which is required for stable interaction between U2 and the branch site. Here we report a 3D cryo-electron microscopy structure of the human 17S U2 snRNP at a core resolution of 4.1 Å and combine it with protein crosslinking data to determine the molecular architecture of this snRNP. Our structure reveals that SF3B1
HEAT
interacts with PRP5 and TAT-SF1, and maintains its open conformation in U2 snRNP, and that U2 snRNA forms a BSL that is sandwiched between PRP5, TAT-SF1 and SF3B1
HEAT
. Thus, substantial remodelling of the BSL and displacement of BSL-interacting proteins must occur to allow formation of the U2–branch-site helix. Our studies provide a structural explanation of why TAT-SF1 must be displaced before the stable addition of U2 to the spliceosome, and identify RNP rearrangements facilitated by PRP5 that are required for stable interaction between U2 and the branch site.
The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements. |
doi_str_mv | 10.1038/s41586-020-2344-3 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2409650917</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2425005665</sourcerecordid><originalsourceid>FETCH-LOGICAL-c452t-9ea3572243777eaf5cf057bef2b7fb2203c9210802dfd8aab726e61e46ad44083</originalsourceid><addsrcrecordid>eNp1kMtOwzAQRS0EoqXwAWxQJDZsAuPxK1kixEsqDwFdW47j0FZpUuxkwd_jKgUkJFazmDN3Zg4hxxTOKbDsInAqMpkCQoqM85TtkDHlSqZcZmqXjAEwSyFjckQOQlgCgKCK75MRQ55zADkm8NDWzva18Ynxdr7onO1675K2Srq5S-b9yjQJVa_JDJPQvDw-H5K9ytTBHW3rhMxurt-u7tLp0-391eU0tVxgl-bOMKEQOVNKOVMJW4FQhauwUFWBCMzmSCEDLKsyM6ZQKJ2kjktTch5vnpCzIXft24_ehU6vFsG6ujaNa_ugkUMuBeRURfT0D7pse9_E6yKFIn4tpYgUHSjr2xC8q_TaL1bGf2oKeqNTDzp11Kk3OjWLMyfb5L5YufJn4ttfBHAAQmw1787_rv4_9Qv7DXwy</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2425005665</pqid></control><display><type>article</type><title>Molecular architecture of the human 17S U2 snRNP</title><source>MEDLINE</source><source>Nature</source><source>Alma/SFX Local Collection</source><creator>Zhang, Zhenwei ; Will, Cindy L. ; Bertram, Karl ; Dybkov, Olexandr ; Hartmuth, Klaus ; Agafonov, Dmitry E. ; Hofele, Romina ; Urlaub, Henning ; Kastner, Berthold ; Lührmann, Reinhard ; Stark, Holger</creator><creatorcontrib>Zhang, Zhenwei ; Will, Cindy L. ; Bertram, Karl ; Dybkov, Olexandr ; Hartmuth, Klaus ; Agafonov, Dmitry E. ; Hofele, Romina ; Urlaub, Henning ; Kastner, Berthold ; Lührmann, Reinhard ; Stark, Holger</creatorcontrib><description>The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing
1
. Stable addition of U2 during early spliceosome formation requires the DEAD-box ATPase PRP5
2
–
7
. Yeast U2 small nuclear RNA (snRNA) nucleotides that form base pairs with the branch site are initially sequestered in a branchpoint-interacting stem–loop (BSL)
8
, but whether the human U2 snRNA folds in a similar manner is unknown. The U2 SF3B1 protein, a common mutational target in haematopoietic cancers
9
, contains a HEAT domain (SF3B1
HEAT
) with an open conformation in isolated SF3b
10
, but a closed conformation in spliceosomes
11
, which is required for stable interaction between U2 and the branch site. Here we report a 3D cryo-electron microscopy structure of the human 17S U2 snRNP at a core resolution of 4.1 Å and combine it with protein crosslinking data to determine the molecular architecture of this snRNP. Our structure reveals that SF3B1
HEAT
interacts with PRP5 and TAT-SF1, and maintains its open conformation in U2 snRNP, and that U2 snRNA forms a BSL that is sandwiched between PRP5, TAT-SF1 and SF3B1
HEAT
. Thus, substantial remodelling of the BSL and displacement of BSL-interacting proteins must occur to allow formation of the U2–branch-site helix. Our studies provide a structural explanation of why TAT-SF1 must be displaced before the stable addition of U2 to the spliceosome, and identify RNP rearrangements facilitated by PRP5 that are required for stable interaction between U2 and the branch site.
The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/s41586-020-2344-3</identifier><identifier>PMID: 32494006</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/28 ; 631/337/1645/1792 ; 631/45/535/1258/1259 ; Adenosine ; Adenosine triphosphatase ; Architecture ; Base Sequence ; Crosslinking ; Cryoelectron Microscopy ; DEAD-box RNA Helicases - chemistry ; DEAD-box RNA Helicases - metabolism ; Electron microscopy ; HeLa Cells ; Humanities and Social Sciences ; Humans ; Microscopy ; Models, Molecular ; Molecular structure ; mRNA ; multidisciplinary ; Mutation ; Nucleotides ; Phosphoproteins - chemistry ; Phosphoproteins - metabolism ; Protein Binding ; Protein Conformation ; Protein structure ; Proteins ; Ribonucleoprotein, U2 Small Nuclear - chemistry ; Ribonucleoprotein, U2 Small Nuclear - genetics ; Ribonucleoprotein, U2 Small Nuclear - metabolism ; Ribonucleoprotein, U2 Small Nuclear - ultrastructure ; Ribonucleoproteins (small nuclear) ; Ribonucleoproteins (U2 small nuclear) ; RNA Splicing Factors - chemistry ; RNA Splicing Factors - metabolism ; Science ; Science (multidisciplinary) ; snRNA ; Spliceosomes ; Splicing ; Trans-Activators - chemistry ; Trans-Activators - metabolism ; Yeasts</subject><ispartof>Nature (London), 2020-07, Vol.583 (7815), p.310-313</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>Copyright Nature Publishing Group Jul 9, 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-9ea3572243777eaf5cf057bef2b7fb2203c9210802dfd8aab726e61e46ad44083</citedby><cites>FETCH-LOGICAL-c452t-9ea3572243777eaf5cf057bef2b7fb2203c9210802dfd8aab726e61e46ad44083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32494006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Zhenwei</creatorcontrib><creatorcontrib>Will, Cindy L.</creatorcontrib><creatorcontrib>Bertram, Karl</creatorcontrib><creatorcontrib>Dybkov, Olexandr</creatorcontrib><creatorcontrib>Hartmuth, Klaus</creatorcontrib><creatorcontrib>Agafonov, Dmitry E.</creatorcontrib><creatorcontrib>Hofele, Romina</creatorcontrib><creatorcontrib>Urlaub, Henning</creatorcontrib><creatorcontrib>Kastner, Berthold</creatorcontrib><creatorcontrib>Lührmann, Reinhard</creatorcontrib><creatorcontrib>Stark, Holger</creatorcontrib><title>Molecular architecture of the human 17S U2 snRNP</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing
1
. Stable addition of U2 during early spliceosome formation requires the DEAD-box ATPase PRP5
2
–
7
. Yeast U2 small nuclear RNA (snRNA) nucleotides that form base pairs with the branch site are initially sequestered in a branchpoint-interacting stem–loop (BSL)
8
, but whether the human U2 snRNA folds in a similar manner is unknown. The U2 SF3B1 protein, a common mutational target in haematopoietic cancers
9
, contains a HEAT domain (SF3B1
HEAT
) with an open conformation in isolated SF3b
10
, but a closed conformation in spliceosomes
11
, which is required for stable interaction between U2 and the branch site. Here we report a 3D cryo-electron microscopy structure of the human 17S U2 snRNP at a core resolution of 4.1 Å and combine it with protein crosslinking data to determine the molecular architecture of this snRNP. Our structure reveals that SF3B1
HEAT
interacts with PRP5 and TAT-SF1, and maintains its open conformation in U2 snRNP, and that U2 snRNA forms a BSL that is sandwiched between PRP5, TAT-SF1 and SF3B1
HEAT
. Thus, substantial remodelling of the BSL and displacement of BSL-interacting proteins must occur to allow formation of the U2–branch-site helix. Our studies provide a structural explanation of why TAT-SF1 must be displaced before the stable addition of U2 to the spliceosome, and identify RNP rearrangements facilitated by PRP5 that are required for stable interaction between U2 and the branch site.
The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements.</description><subject>101/28</subject><subject>631/337/1645/1792</subject><subject>631/45/535/1258/1259</subject><subject>Adenosine</subject><subject>Adenosine triphosphatase</subject><subject>Architecture</subject><subject>Base Sequence</subject><subject>Crosslinking</subject><subject>Cryoelectron Microscopy</subject><subject>DEAD-box RNA Helicases - chemistry</subject><subject>DEAD-box RNA Helicases - metabolism</subject><subject>Electron microscopy</subject><subject>HeLa Cells</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Microscopy</subject><subject>Models, Molecular</subject><subject>Molecular structure</subject><subject>mRNA</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Nucleotides</subject><subject>Phosphoproteins - chemistry</subject><subject>Phosphoproteins - metabolism</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Protein structure</subject><subject>Proteins</subject><subject>Ribonucleoprotein, U2 Small Nuclear - chemistry</subject><subject>Ribonucleoprotein, U2 Small Nuclear - genetics</subject><subject>Ribonucleoprotein, U2 Small Nuclear - metabolism</subject><subject>Ribonucleoprotein, U2 Small Nuclear - ultrastructure</subject><subject>Ribonucleoproteins (small nuclear)</subject><subject>Ribonucleoproteins (U2 small nuclear)</subject><subject>RNA Splicing Factors - chemistry</subject><subject>RNA Splicing Factors - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>snRNA</subject><subject>Spliceosomes</subject><subject>Splicing</subject><subject>Trans-Activators - chemistry</subject><subject>Trans-Activators - metabolism</subject><subject>Yeasts</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kMtOwzAQRS0EoqXwAWxQJDZsAuPxK1kixEsqDwFdW47j0FZpUuxkwd_jKgUkJFazmDN3Zg4hxxTOKbDsInAqMpkCQoqM85TtkDHlSqZcZmqXjAEwSyFjckQOQlgCgKCK75MRQ55zADkm8NDWzva18Ynxdr7onO1675K2Srq5S-b9yjQJVa_JDJPQvDw-H5K9ytTBHW3rhMxurt-u7tLp0-391eU0tVxgl-bOMKEQOVNKOVMJW4FQhauwUFWBCMzmSCEDLKsyM6ZQKJ2kjktTch5vnpCzIXft24_ehU6vFsG6ujaNa_ugkUMuBeRURfT0D7pse9_E6yKFIn4tpYgUHSjr2xC8q_TaL1bGf2oKeqNTDzp11Kk3OjWLMyfb5L5YufJn4ttfBHAAQmw1787_rv4_9Qv7DXwy</recordid><startdate>20200709</startdate><enddate>20200709</enddate><creator>Zhang, Zhenwei</creator><creator>Will, Cindy L.</creator><creator>Bertram, Karl</creator><creator>Dybkov, Olexandr</creator><creator>Hartmuth, Klaus</creator><creator>Agafonov, Dmitry E.</creator><creator>Hofele, Romina</creator><creator>Urlaub, Henning</creator><creator>Kastner, Berthold</creator><creator>Lührmann, Reinhard</creator><creator>Stark, Holger</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope></search><sort><creationdate>20200709</creationdate><title>Molecular architecture of the human 17S U2 snRNP</title><author>Zhang, Zhenwei ; Will, Cindy L. ; Bertram, Karl ; Dybkov, Olexandr ; Hartmuth, Klaus ; Agafonov, Dmitry E. ; Hofele, Romina ; Urlaub, Henning ; Kastner, Berthold ; Lührmann, Reinhard ; Stark, Holger</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-9ea3572243777eaf5cf057bef2b7fb2203c9210802dfd8aab726e61e46ad44083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>101/28</topic><topic>631/337/1645/1792</topic><topic>631/45/535/1258/1259</topic><topic>Adenosine</topic><topic>Adenosine triphosphatase</topic><topic>Architecture</topic><topic>Base Sequence</topic><topic>Crosslinking</topic><topic>Cryoelectron Microscopy</topic><topic>DEAD-box RNA Helicases - chemistry</topic><topic>DEAD-box RNA Helicases - metabolism</topic><topic>Electron microscopy</topic><topic>HeLa Cells</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Microscopy</topic><topic>Models, Molecular</topic><topic>Molecular structure</topic><topic>mRNA</topic><topic>multidisciplinary</topic><topic>Mutation</topic><topic>Nucleotides</topic><topic>Phosphoproteins - chemistry</topic><topic>Phosphoproteins - metabolism</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Protein structure</topic><topic>Proteins</topic><topic>Ribonucleoprotein, U2 Small Nuclear - chemistry</topic><topic>Ribonucleoprotein, U2 Small Nuclear - genetics</topic><topic>Ribonucleoprotein, U2 Small Nuclear - metabolism</topic><topic>Ribonucleoprotein, U2 Small Nuclear - ultrastructure</topic><topic>Ribonucleoproteins (small nuclear)</topic><topic>Ribonucleoproteins (U2 small nuclear)</topic><topic>RNA Splicing Factors - chemistry</topic><topic>RNA Splicing Factors - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>snRNA</topic><topic>Spliceosomes</topic><topic>Splicing</topic><topic>Trans-Activators - chemistry</topic><topic>Trans-Activators - metabolism</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zhenwei</creatorcontrib><creatorcontrib>Will, Cindy L.</creatorcontrib><creatorcontrib>Bertram, Karl</creatorcontrib><creatorcontrib>Dybkov, Olexandr</creatorcontrib><creatorcontrib>Hartmuth, Klaus</creatorcontrib><creatorcontrib>Agafonov, Dmitry E.</creatorcontrib><creatorcontrib>Hofele, Romina</creatorcontrib><creatorcontrib>Urlaub, Henning</creatorcontrib><creatorcontrib>Kastner, Berthold</creatorcontrib><creatorcontrib>Lührmann, Reinhard</creatorcontrib><creatorcontrib>Stark, Holger</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Database (1962 - current)</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database (ProQuest)</collection><collection>ProQuest research library</collection><collection>ProQuest Science Journals</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials science collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Zhenwei</au><au>Will, Cindy L.</au><au>Bertram, Karl</au><au>Dybkov, Olexandr</au><au>Hartmuth, Klaus</au><au>Agafonov, Dmitry E.</au><au>Hofele, Romina</au><au>Urlaub, Henning</au><au>Kastner, Berthold</au><au>Lührmann, Reinhard</au><au>Stark, Holger</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular architecture of the human 17S U2 snRNP</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2020-07-09</date><risdate>2020</risdate><volume>583</volume><issue>7815</issue><spage>310</spage><epage>313</epage><pages>310-313</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>The U2 small nuclear ribonucleoprotein (snRNP) has an essential role in the selection of the precursor mRNA branch-site adenosine, the nucleophile for the first step of splicing
1
. Stable addition of U2 during early spliceosome formation requires the DEAD-box ATPase PRP5
2
–
7
. Yeast U2 small nuclear RNA (snRNA) nucleotides that form base pairs with the branch site are initially sequestered in a branchpoint-interacting stem–loop (BSL)
8
, but whether the human U2 snRNA folds in a similar manner is unknown. The U2 SF3B1 protein, a common mutational target in haematopoietic cancers
9
, contains a HEAT domain (SF3B1
HEAT
) with an open conformation in isolated SF3b
10
, but a closed conformation in spliceosomes
11
, which is required for stable interaction between U2 and the branch site. Here we report a 3D cryo-electron microscopy structure of the human 17S U2 snRNP at a core resolution of 4.1 Å and combine it with protein crosslinking data to determine the molecular architecture of this snRNP. Our structure reveals that SF3B1
HEAT
interacts with PRP5 and TAT-SF1, and maintains its open conformation in U2 snRNP, and that U2 snRNA forms a BSL that is sandwiched between PRP5, TAT-SF1 and SF3B1
HEAT
. Thus, substantial remodelling of the BSL and displacement of BSL-interacting proteins must occur to allow formation of the U2–branch-site helix. Our studies provide a structural explanation of why TAT-SF1 must be displaced before the stable addition of U2 to the spliceosome, and identify RNP rearrangements facilitated by PRP5 that are required for stable interaction between U2 and the branch site.
The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32494006</pmid><doi>10.1038/s41586-020-2344-3</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0028-0836 |
ispartof | Nature (London), 2020-07, Vol.583 (7815), p.310-313 |
issn | 0028-0836 1476-4687 |
language | eng |
recordid | cdi_proquest_miscellaneous_2409650917 |
source | MEDLINE; Nature; Alma/SFX Local Collection |
subjects | 101/28 631/337/1645/1792 631/45/535/1258/1259 Adenosine Adenosine triphosphatase Architecture Base Sequence Crosslinking Cryoelectron Microscopy DEAD-box RNA Helicases - chemistry DEAD-box RNA Helicases - metabolism Electron microscopy HeLa Cells Humanities and Social Sciences Humans Microscopy Models, Molecular Molecular structure mRNA multidisciplinary Mutation Nucleotides Phosphoproteins - chemistry Phosphoproteins - metabolism Protein Binding Protein Conformation Protein structure Proteins Ribonucleoprotein, U2 Small Nuclear - chemistry Ribonucleoprotein, U2 Small Nuclear - genetics Ribonucleoprotein, U2 Small Nuclear - metabolism Ribonucleoprotein, U2 Small Nuclear - ultrastructure Ribonucleoproteins (small nuclear) Ribonucleoproteins (U2 small nuclear) RNA Splicing Factors - chemistry RNA Splicing Factors - metabolism Science Science (multidisciplinary) snRNA Spliceosomes Splicing Trans-Activators - chemistry Trans-Activators - metabolism Yeasts |
title | Molecular architecture of the human 17S U2 snRNP |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T09%3A35%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Molecular%20architecture%20of%20the%20human%2017S%20U2%20snRNP&rft.jtitle=Nature%20(London)&rft.au=Zhang,%20Zhenwei&rft.date=2020-07-09&rft.volume=583&rft.issue=7815&rft.spage=310&rft.epage=313&rft.pages=310-313&rft.issn=0028-0836&rft.eissn=1476-4687&rft_id=info:doi/10.1038/s41586-020-2344-3&rft_dat=%3Cproquest_cross%3E2425005665%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2425005665&rft_id=info:pmid/32494006&rfr_iscdi=true |