The RNA Binding Protein Pub1 Modulates the Stability of Transcripts Containing Upstream Open Reading Frames
The nonsense-mediated mRNA decay (NMD) pathway functions to degrade transcripts containing nonsense codons. Transcripts containing mutations that insert an upstream open reading frame (uORF) in the 5′-UTR are degraded through NMD. However, several naturally occurring uORF-containing transcripts are...
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| Veröffentlicht in: | Cell 2000-06, Vol.101 (7), p.741-751 |
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| creator | Ruiz-Echevarría, Maria J Peltz, Stuart W |
| description | The nonsense-mediated mRNA decay (NMD) pathway functions to degrade transcripts containing nonsense codons. Transcripts containing mutations that insert an upstream open reading frame (uORF) in the 5′-UTR are degraded through NMD. However, several naturally occurring uORF-containing transcripts are resistant to NMD. Here we demonstrate that the GCN4 and YAP1 mRNAs, which contain uORFs, harbor a stabilizer element (STE) that prevents rapid NMD by interacting with the RNA binding protein Pub1. Conversely, a uORF-containing mRNA that lacks an STE, such as CPA1, is degraded by the NMD pathway. These results indicate that uORFs can play a pivotal role regulating both translation and turnover and that the Pub1p is a critical factor that modulates the stability of uORF-containing transcripts. |
| doi_str_mv | 10.1016/S0092-8674(00)80886-7 |
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Transcripts containing mutations that insert an upstream open reading frame (uORF) in the 5′-UTR are degraded through NMD. However, several naturally occurring uORF-containing transcripts are resistant to NMD. Here we demonstrate that the GCN4 and YAP1 mRNAs, which contain uORFs, harbor a stabilizer element (STE) that prevents rapid NMD by interacting with the RNA binding protein Pub1. Conversely, a uORF-containing mRNA that lacks an STE, such as CPA1, is degraded by the NMD pathway. These results indicate that uORFs can play a pivotal role regulating both translation and turnover and that the Pub1p is a critical factor that modulates the stability of uORF-containing transcripts.</description><subject>5' Untranslated Regions - genetics</subject><subject>Base Sequence</subject><subject>Fungal Proteins - genetics</subject><subject>GCN4 gene</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Molecular Sequence Data</subject><subject>Open Reading Frames - genetics</subject><subject>Poly(A)-Binding Proteins</subject><subject>Pub1 protein</subject><subject>RNA, Fungal - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA-binding protein</subject><subject>RNA-Binding Proteins - genetics</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae Proteins</subject><subject>Transcription, Genetic</subject><subject>YAP1 gene</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EosvCTwD5hOAQGCexxzmhsqKAVGjVbs-W48yCIXFS20Hqvye7WyFu1Rzm8r15o_cYeyngnQCh3l8DNGWhFdZvAN5q0FoV-IitBDRY1ALLx2z1Dzlhz1L6BQBaSvmUnQjQTYm1XLHf25_Er76f8o8-dD784JdxzOQDv5xbwb-N3dzbTInnBbvOtvW9z3d83PFttCG56Kec-GYM2fqwl99MKUeyA7-YKPArsoejZ9EOlJ6zJzvbJ3pxv9fs5uzTdvOlOL_4_HVzel44KTEXhFjpZdCBkpJUZalDciiaStkOta4qrbFsm87tWmilxrpWGoWyVNsFrtbs9fHuFMfbmVI2g0-O-t4GGudkUJR1I6R6EBS4PFQuvmsmj6CLY0qRdmaKfrDxzggw-zrMoQ6zz9oAmEMdBhfdq3uDuR2o-091zH8BPhwBWvL44yma5DwFR52P5LLpRv-AxV_rU5l7</recordid><startdate>20000623</startdate><enddate>20000623</enddate><creator>Ruiz-Echevarría, Maria J</creator><creator>Peltz, Stuart W</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>20000623</creationdate><title>The RNA Binding Protein Pub1 Modulates the Stability of Transcripts Containing Upstream Open Reading Frames</title><author>Ruiz-Echevarría, Maria J ; Peltz, Stuart W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-e77383837c0655e63aed7ec71936ad788338872b9dcfb0b5874468716ae4a3ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>5' Untranslated Regions - genetics</topic><topic>Base Sequence</topic><topic>Fungal Proteins - genetics</topic><topic>GCN4 gene</topic><topic>Gene Expression Regulation, Fungal</topic><topic>Molecular Sequence Data</topic><topic>Open Reading Frames - genetics</topic><topic>Poly(A)-Binding Proteins</topic><topic>Pub1 protein</topic><topic>RNA, Fungal - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA-binding protein</topic><topic>RNA-Binding Proteins - genetics</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Transcription, Genetic</topic><topic>YAP1 gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruiz-Echevarría, Maria J</creatorcontrib><creatorcontrib>Peltz, Stuart W</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>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ruiz-Echevarría, Maria J</au><au>Peltz, Stuart W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The RNA Binding Protein Pub1 Modulates the Stability of Transcripts Containing Upstream Open Reading Frames</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2000-06-23</date><risdate>2000</risdate><volume>101</volume><issue>7</issue><spage>741</spage><epage>751</epage><pages>741-751</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>The nonsense-mediated mRNA decay (NMD) pathway functions to degrade transcripts containing nonsense codons. Transcripts containing mutations that insert an upstream open reading frame (uORF) in the 5′-UTR are degraded through NMD. However, several naturally occurring uORF-containing transcripts are resistant to NMD. Here we demonstrate that the GCN4 and YAP1 mRNAs, which contain uORFs, harbor a stabilizer element (STE) that prevents rapid NMD by interacting with the RNA binding protein Pub1. Conversely, a uORF-containing mRNA that lacks an STE, such as CPA1, is degraded by the NMD pathway. These results indicate that uORFs can play a pivotal role regulating both translation and turnover and that the Pub1p is a critical factor that modulates the stability of uORF-containing transcripts.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>10892745</pmid><doi>10.1016/S0092-8674(00)80886-7</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals |
| subjects | 5' Untranslated Regions - genetics Base Sequence Fungal Proteins - genetics GCN4 gene Gene Expression Regulation, Fungal Molecular Sequence Data Open Reading Frames - genetics Poly(A)-Binding Proteins Pub1 protein RNA, Fungal - genetics RNA, Messenger - genetics RNA-binding protein RNA-Binding Proteins - genetics Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Transcription, Genetic YAP1 gene |
| title | The RNA Binding Protein Pub1 Modulates the Stability of Transcripts Containing Upstream Open Reading Frames |
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