Involvement of SR Proteins in mRNA Surveillance
Nonsense mutations influence several aspects of gene expression, including mRNA stability and splicing fidelity, but the mechanism by which premature termination codons (PTCs) can apparently affect splice-site selection remains elusive. We used a model human β-globin gene with duplicated 5′ splice s...
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| Veröffentlicht in: | Molecular cell 2004-11, Vol.16 (4), p.597-607 |
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| creator | Zhang, Zuo Krainer, Adrian R. |
| description | Nonsense mutations influence several aspects of gene expression, including mRNA stability and splicing fidelity, but the mechanism by which premature termination codons (PTCs) can apparently affect splice-site selection remains elusive. We used a model human β-globin gene with duplicated 5′ splice sites (5′ss) and found that PTCs inserted between the two 5′ss do not directly influence splicing in this system. Instead, their apparent effect on 5′ss selection in vivo is an indirect result of nonsense-mediated mRNA decay (NMD), as conditions that eliminated NMD also abrogated the effect on splicing. Remarkably, we found an unexpected function of SR proteins in targeting several mRNAs with PTCs to the NMD pathway. Overexpression of various SR proteins strongly enhanced NMD, and this effect required an RS domain. Our data argue against a universal role of PTCs in regulating pre-mRNA splicing and reveal an additional function of SR proteins in eukaryotic gene expression. |
| doi_str_mv | 10.1016/j.molcel.2004.10.031 |
| format | Article |
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Our data argue against a universal role of PTCs in regulating pre-mRNA splicing and reveal an additional function of SR proteins in eukaryotic gene expression.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2004.10.031</identifier><identifier>PMID: 15546619</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blotting, Western ; Cercopithecus aethiops ; Codon, Nonsense ; Codon, Terminator ; COS Cells ; Exons ; Gene Expression Regulation ; Globins - genetics ; HeLa Cells ; Humans ; Introns ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Point Mutation ; RNA Interference ; RNA Precursors - metabolism ; RNA Splicing ; RNA Stability ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA-Binding Proteins ; Serine-Arginine Splicing Factors</subject><ispartof>Molecular cell, 2004-11, Vol.16 (4), p.597-607</ispartof><rights>2004 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-efeaa6161f558cea69ba2f0ab69145a3c3c09d487f13f8c3c81891886292a4f63</citedby><cites>FETCH-LOGICAL-c435t-efeaa6161f558cea69ba2f0ab69145a3c3c09d487f13f8c3c81891886292a4f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molcel.2004.10.031$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15546619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Zuo</creatorcontrib><creatorcontrib>Krainer, Adrian R.</creatorcontrib><title>Involvement of SR Proteins in mRNA Surveillance</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>Nonsense mutations influence several aspects of gene expression, including mRNA stability and splicing fidelity, but the mechanism by which premature termination codons (PTCs) can apparently affect splice-site selection remains elusive. We used a model human β-globin gene with duplicated 5′ splice sites (5′ss) and found that PTCs inserted between the two 5′ss do not directly influence splicing in this system. Instead, their apparent effect on 5′ss selection in vivo is an indirect result of nonsense-mediated mRNA decay (NMD), as conditions that eliminated NMD also abrogated the effect on splicing. Remarkably, we found an unexpected function of SR proteins in targeting several mRNAs with PTCs to the NMD pathway. Overexpression of various SR proteins strongly enhanced NMD, and this effect required an RS domain. Our data argue against a universal role of PTCs in regulating pre-mRNA splicing and reveal an additional function of SR proteins in eukaryotic gene expression.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cercopithecus aethiops</subject><subject>Codon, Nonsense</subject><subject>Codon, Terminator</subject><subject>COS Cells</subject><subject>Exons</subject><subject>Gene Expression Regulation</subject><subject>Globins - genetics</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Introns</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Point Mutation</subject><subject>RNA Interference</subject><subject>RNA Precursors - metabolism</subject><subject>RNA Splicing</subject><subject>RNA Stability</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA-Binding Proteins</subject><subject>Serine-Arginine Splicing Factors</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtKAzEUQIMotlb_QGRW7tomM0km2Qil-CgUlVbXIU1vIGVmUpOZAf_elBbc6So3l3NfB6FbgicEEz7dTWpfGagmOcY0pSa4IGdoSLAsx5Rwen6K85KzAbqKcYcxoUzISzQgjFHOiRyi6aLpfdVDDU2beZutV9l78C24JmauyerV6yxbd6EHV1W6MXCNLqyuItyc3hH6fHr8mL-Ml2_Pi_lsOTa0YO0YLGjNCSeWMWFAc7nRucV6w2XaQRemMFhuqSgtKaxIP0GEJELwXOaaWl6M0P2x7z74rw5iq2oX07VpCfBdVLzEglMs_wVJWbKSsTyB9Aia4GMMYNU-uFqHb0WwOhhVO3U0qg5GD9lkNJXdnfp3mxq2v0UnhQl4OAKQdPQOgorGQVK1dQFMq7be_T3hBzIAh0I</recordid><startdate>20041119</startdate><enddate>20041119</enddate><creator>Zhang, Zuo</creator><creator>Krainer, Adrian R.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20041119</creationdate><title>Involvement of SR Proteins in mRNA Surveillance</title><author>Zhang, Zuo ; Krainer, Adrian R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-efeaa6161f558cea69ba2f0ab69145a3c3c09d487f13f8c3c81891886292a4f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cercopithecus aethiops</topic><topic>Codon, Nonsense</topic><topic>Codon, Terminator</topic><topic>COS Cells</topic><topic>Exons</topic><topic>Gene Expression Regulation</topic><topic>Globins - genetics</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Introns</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Point Mutation</topic><topic>RNA Interference</topic><topic>RNA Precursors - metabolism</topic><topic>RNA Splicing</topic><topic>RNA Stability</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA-Binding Proteins</topic><topic>Serine-Arginine Splicing Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zuo</creatorcontrib><creatorcontrib>Krainer, Adrian R.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Zuo</au><au>Krainer, Adrian R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of SR Proteins in mRNA Surveillance</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2004-11-19</date><risdate>2004</risdate><volume>16</volume><issue>4</issue><spage>597</spage><epage>607</epage><pages>597-607</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>Nonsense mutations influence several aspects of gene expression, including mRNA stability and splicing fidelity, but the mechanism by which premature termination codons (PTCs) can apparently affect splice-site selection remains elusive. 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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Animals Blotting, Western Cercopithecus aethiops Codon, Nonsense Codon, Terminator COS Cells Exons Gene Expression Regulation Globins - genetics HeLa Cells Humans Introns Nuclear Proteins - genetics Nuclear Proteins - metabolism Point Mutation RNA Interference RNA Precursors - metabolism RNA Splicing RNA Stability RNA, Messenger - genetics RNA, Messenger - metabolism RNA-Binding Proteins Serine-Arginine Splicing Factors |
| title | Involvement of SR Proteins in mRNA Surveillance |
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