Distinct Domains of Splicing Factor Prp8 Mediate Different Aspects of Spliceosome Activation
Prp8 is the largest and most highly conserved protein in the spliceosome yet its mechanism of function is poorly understood. Our previous studies implicate Prp8 in control of spliceosome activation for the first catalytic step of splicing, because substitutions in five distinct regions (a-e) of Prp8...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2002-07, Vol.99 (14), p.9145-9149 |
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| creator | Kuhn, Andreas N. Reichl, Elizabeth M. Brow, David A. |
| description | Prp8 is the largest and most highly conserved protein in the spliceosome yet its mechanism of function is poorly understood. Our previous studies implicate Prp8 in control of spliceosome activation for the first catalytic step of splicing, because substitutions in five distinct regions (a-e) of Prp8 suppress a cold-sensitive block to activation caused by a mutation in U4 RNA. Catalytic activation of the spliceosome is thought to require unwinding of the U1 RNA/5′ splice site and U4/U6 RNA helices by the Prp28 and Prp44/Brr2 DExD/H-box helicases, respectively. Here we show that mutations in regions a, d, and e of Prp8 exhibit allele-specific genetic interactions with mutations in Prp28, Prp44/Brr2, and U6 RNA, respectively. These results indicate that Prp8 coordinates multiple processes in spliceosome activation and enable an initial correlation of Prp8 structure and function. Furthermore, additional genetic interactions with U4-cs1 support a two-state model for this RNA conformational switch and implicate another splicing factor, Prp31, in Prp8-mediated spliceosome activation. |
| doi_str_mv | 10.1073/pnas.102304299 |
| format | Article |
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Our previous studies implicate Prp8 in control of spliceosome activation for the first catalytic step of splicing, because substitutions in five distinct regions (a-e) of Prp8 suppress a cold-sensitive block to activation caused by a mutation in U4 RNA. Catalytic activation of the spliceosome is thought to require unwinding of the U1 RNA/5′ splice site and U4/U6 RNA helices by the Prp28 and Prp44/Brr2 DExD/H-box helicases, respectively. Here we show that mutations in regions a, d, and e of Prp8 exhibit allele-specific genetic interactions with mutations in Prp28, Prp44/Brr2, and U6 RNA, respectively. These results indicate that Prp8 coordinates multiple processes in spliceosome activation and enable an initial correlation of Prp8 structure and function. Furthermore, additional genetic interactions with U4-cs1 support a two-state model for this RNA conformational switch and implicate another splicing factor, Prp31, in Prp8-mediated spliceosome activation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.102304299</identifier><identifier>PMID: 12087126</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Alleles ; Amino Acid Sequence ; Amino acids ; Base Sequence ; Biochemistry ; Biological Sciences ; Cold Temperature ; DEAD-box RNA Helicases ; Fungal Proteins - chemistry ; Fungal Proteins - genetics ; Fungal Proteins - metabolism ; Genes ; Genetic mutation ; Medical genetics ; Molecular Sequence Data ; Mutation ; Plasmids ; Protein Structure, Tertiary ; Proteins ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Ribonucleic acid ; Ribonucleoprotein, U4-U6 Small Nuclear ; Ribonucleoprotein, U5 Small Nuclear ; RNA ; RNA Helicases ; RNA Nucleotidyltransferases - genetics ; RNA Nucleotidyltransferases - metabolism ; RNA Splicing ; RNA, Fungal - genetics ; RNA, Fungal - metabolism ; RNA, Small Nuclear - genetics ; RNA, Small Nuclear - metabolism ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins - chemistry ; Saccharomyces cerevisiae Proteins - genetics ; Saccharomyces cerevisiae Proteins - metabolism ; Sequence Homology, Amino Acid ; Spliceosomes ; Spliceosomes - metabolism ; Splicing ; Yeasts</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2002-07, Vol.99 (14), p.9145-9149</ispartof><rights>Copyright 1993-2002 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jul 9, 2002</rights><rights>Copyright © 2002, The National Academy of Sciences 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-e3c69ff9677d9700d0ce97045578e3d7a4208ba796be73ea914f2b03a6864c043</citedby><cites>FETCH-LOGICAL-c519t-e3c69ff9677d9700d0ce97045578e3d7a4208ba796be73ea914f2b03a6864c043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/99/14.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3059166$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3059166$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12087126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuhn, Andreas N.</creatorcontrib><creatorcontrib>Reichl, Elizabeth M.</creatorcontrib><creatorcontrib>Brow, David A.</creatorcontrib><title>Distinct Domains of Splicing Factor Prp8 Mediate Different Aspects of Spliceosome Activation</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Prp8 is the largest and most highly conserved protein in the spliceosome yet its mechanism of function is poorly understood. Our previous studies implicate Prp8 in control of spliceosome activation for the first catalytic step of splicing, because substitutions in five distinct regions (a-e) of Prp8 suppress a cold-sensitive block to activation caused by a mutation in U4 RNA. Catalytic activation of the spliceosome is thought to require unwinding of the U1 RNA/5′ splice site and U4/U6 RNA helices by the Prp28 and Prp44/Brr2 DExD/H-box helicases, respectively. Here we show that mutations in regions a, d, and e of Prp8 exhibit allele-specific genetic interactions with mutations in Prp28, Prp44/Brr2, and U6 RNA, respectively. These results indicate that Prp8 coordinates multiple processes in spliceosome activation and enable an initial correlation of Prp8 structure and function. Furthermore, additional genetic interactions with U4-cs1 support a two-state model for this RNA conformational switch and implicate another splicing factor, Prp31, in Prp8-mediated spliceosome activation.</description><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Base Sequence</subject><subject>Biochemistry</subject><subject>Biological Sciences</subject><subject>Cold Temperature</subject><subject>DEAD-box RNA Helicases</subject><subject>Fungal Proteins - chemistry</subject><subject>Fungal Proteins - genetics</subject><subject>Fungal Proteins - metabolism</subject><subject>Genes</subject><subject>Genetic mutation</subject><subject>Medical genetics</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Plasmids</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Ribonucleic acid</subject><subject>Ribonucleoprotein, U4-U6 Small Nuclear</subject><subject>Ribonucleoprotein, U5 Small Nuclear</subject><subject>RNA</subject><subject>RNA Helicases</subject><subject>RNA Nucleotidyltransferases - genetics</subject><subject>RNA Nucleotidyltransferases - metabolism</subject><subject>RNA Splicing</subject><subject>RNA, Fungal - genetics</subject><subject>RNA, Fungal - metabolism</subject><subject>RNA, Small Nuclear - genetics</subject><subject>RNA, Small Nuclear - metabolism</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - chemistry</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Spliceosomes</subject><subject>Spliceosomes - metabolism</subject><subject>Splicing</subject><subject>Yeasts</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks2LFDEQxYMo7rh69STSeNBTr5WP7iQHD8OOq8KKgnoTQiZdvWbo6bRJetH_3gwzzq4ieAgVqN8rXuqFkMcUzihI_nIabSo3xkEwre-QBQVN61ZouEsWAEzWSjBxQh6ktAEA3Si4T04oAyUpaxfk68qn7EeXq1XYWj-mKvTVp2nwzo9X1YV1OcTqY5xU9R47bzNWK9_3GHHM1TJN6PKNAkMKW6yWLvtrm30YH5J7vR0SPjrUU_Ll4vXn87f15Yc3786Xl7VrqM41ctfqvtetlJ2WAB04LFU0jVTIO2lFsbu2UrdrlBytpqJna-C2Va1wIPgpebWfO83rLXaumIt2MFP0Wxt_mmC9-bMz-m_mKlwbyjgFVfTPD_oYvs-Ystn65HAY7IhhTkZSpQAE_BekSnCmGC_gs7_ATZjjWJZgGFCuZTkFOttDLoaUIvZHxxTMLl2zS9cc0y2Cp7ffeYMf4izAiwOwE_5ua22oMGVrjennYcj4I98a9W-yAE_2wCaVL3AkODSati3_BU69wZI</recordid><startdate>20020709</startdate><enddate>20020709</enddate><creator>Kuhn, Andreas N.</creator><creator>Reichl, Elizabeth M.</creator><creator>Brow, David A.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20020709</creationdate><title>Distinct Domains of Splicing Factor Prp8 Mediate Different Aspects of Spliceosome Activation</title><author>Kuhn, Andreas N. ; Reichl, Elizabeth M. ; Brow, David A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-e3c69ff9677d9700d0ce97045578e3d7a4208ba796be73ea914f2b03a6864c043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Amino acids</topic><topic>Base Sequence</topic><topic>Biochemistry</topic><topic>Biological Sciences</topic><topic>Cold Temperature</topic><topic>DEAD-box RNA Helicases</topic><topic>Fungal Proteins - chemistry</topic><topic>Fungal Proteins - genetics</topic><topic>Fungal Proteins - metabolism</topic><topic>Genes</topic><topic>Genetic mutation</topic><topic>Medical genetics</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Plasmids</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Ribonucleic acid</topic><topic>Ribonucleoprotein, U4-U6 Small Nuclear</topic><topic>Ribonucleoprotein, U5 Small Nuclear</topic><topic>RNA</topic><topic>RNA Helicases</topic><topic>RNA Nucleotidyltransferases - genetics</topic><topic>RNA Nucleotidyltransferases - metabolism</topic><topic>RNA Splicing</topic><topic>RNA, Fungal - genetics</topic><topic>RNA, Fungal - metabolism</topic><topic>RNA, Small Nuclear - genetics</topic><topic>RNA, Small Nuclear - metabolism</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - chemistry</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Spliceosomes</topic><topic>Spliceosomes - metabolism</topic><topic>Splicing</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuhn, Andreas N.</creatorcontrib><creatorcontrib>Reichl, Elizabeth M.</creatorcontrib><creatorcontrib>Brow, David A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology 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>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuhn, Andreas N.</au><au>Reichl, Elizabeth M.</au><au>Brow, David A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct Domains of Splicing Factor Prp8 Mediate Different Aspects of Spliceosome Activation</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2002-07-09</date><risdate>2002</risdate><volume>99</volume><issue>14</issue><spage>9145</spage><epage>9149</epage><pages>9145-9149</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Prp8 is the largest and most highly conserved protein in the spliceosome yet its mechanism of function is poorly understood. Our previous studies implicate Prp8 in control of spliceosome activation for the first catalytic step of splicing, because substitutions in five distinct regions (a-e) of Prp8 suppress a cold-sensitive block to activation caused by a mutation in U4 RNA. Catalytic activation of the spliceosome is thought to require unwinding of the U1 RNA/5′ splice site and U4/U6 RNA helices by the Prp28 and Prp44/Brr2 DExD/H-box helicases, respectively. Here we show that mutations in regions a, d, and e of Prp8 exhibit allele-specific genetic interactions with mutations in Prp28, Prp44/Brr2, and U6 RNA, respectively. These results indicate that Prp8 coordinates multiple processes in spliceosome activation and enable an initial correlation of Prp8 structure and function. Furthermore, additional genetic interactions with U4-cs1 support a two-state model for this RNA conformational switch and implicate another splicing factor, Prp31, in Prp8-mediated spliceosome activation.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>12087126</pmid><doi>10.1073/pnas.102304299</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alleles Amino Acid Sequence Amino acids Base Sequence Biochemistry Biological Sciences Cold Temperature DEAD-box RNA Helicases Fungal Proteins - chemistry Fungal Proteins - genetics Fungal Proteins - metabolism Genes Genetic mutation Medical genetics Molecular Sequence Data Mutation Plasmids Protein Structure, Tertiary Proteins Repressor Proteins - genetics Repressor Proteins - metabolism Ribonucleic acid Ribonucleoprotein, U4-U6 Small Nuclear Ribonucleoprotein, U5 Small Nuclear RNA RNA Helicases RNA Nucleotidyltransferases - genetics RNA Nucleotidyltransferases - metabolism RNA Splicing RNA, Fungal - genetics RNA, Fungal - metabolism RNA, Small Nuclear - genetics RNA, Small Nuclear - metabolism Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - chemistry Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Sequence Homology, Amino Acid Spliceosomes Spliceosomes - metabolism Splicing Yeasts |
| title | Distinct Domains of Splicing Factor Prp8 Mediate Different Aspects of Spliceosome Activation |
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