Tat Stimulates Cotranscriptional Capping of HIV mRNA
Here we investigated how capping and methylation of HIV pre-mRNAs are coupled to Pol II elongation. Stable binding of the capping enzyme (Mce1) and cap methyltransferase (Hcm1) to template-engaged Pol II depends on CTD phosphorylation, but not on nascent RNA. Both Mce1 and Hcm1 travel with Pol II du...
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Veröffentlicht in: | Molecular cell 2002-09, Vol.10 (3), p.585-597 |
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creator | Chiu, Ya-Lin Ho, C.Kiong Saha, Nayanendu Schwer, Beate Shuman, Stewart Rana, Tariq M |
description | Here we investigated how capping and methylation of HIV pre-mRNAs are coupled to Pol II elongation. Stable binding of the capping enzyme (Mce1) and cap methyltransferase (Hcm1) to template-engaged Pol II depends on CTD phosphorylation, but not on nascent RNA. Both Mce1 and Hcm1 travel with Pol II during elongation. The capping and methylation reactions cannot occur until the nascent pre-mRNA has attained a chain length of 19–22 nucleotides. HIV pre-mRNAs are capped quantitatively when elongation complexes are halted at promoter-proximal positions, but capping is much less efficient during unimpeded Pol II elongation. Cotranscriptional capping of HIV mRNA is strongly stimulated by Tat, and this stimulation requires the C-terminal segment of Tat that mediates its direct binding to Mce1. Our findings implicate capping in an elongation checkpoint critical to HIV gene expression. |
doi_str_mv | 10.1016/S1097-2765(02)00630-5 |
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Stable binding of the capping enzyme (Mce1) and cap methyltransferase (Hcm1) to template-engaged Pol II depends on CTD phosphorylation, but not on nascent RNA. Both Mce1 and Hcm1 travel with Pol II during elongation. The capping and methylation reactions cannot occur until the nascent pre-mRNA has attained a chain length of 19–22 nucleotides. HIV pre-mRNAs are capped quantitatively when elongation complexes are halted at promoter-proximal positions, but capping is much less efficient during unimpeded Pol II elongation. Cotranscriptional capping of HIV mRNA is strongly stimulated by Tat, and this stimulation requires the C-terminal segment of Tat that mediates its direct binding to Mce1. Our findings implicate capping in an elongation checkpoint critical to HIV gene expression.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/S1097-2765(02)00630-5</identifier><identifier>PMID: 12408826</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Gene Expression Regulation, Viral ; Gene Products, tat - metabolism ; HeLa Cells ; HIV Long Terminal Repeat ; HIV-1 - enzymology ; HIV-1 - genetics ; Humans ; Methylation ; Methyltransferases - genetics ; Methyltransferases - metabolism ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Nucleic Acid Conformation ; Nucleotidyltransferases - genetics ; Nucleotidyltransferases - metabolism ; Promoter Regions, Genetic ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; RNA Caps - metabolism ; RNA Polymerase II - metabolism ; RNA Processing, Post-Transcriptional ; RNA, Viral - metabolism ; tat Gene Products, Human Immunodeficiency Virus ; Transcription, Genetic ; Viral Proteins - genetics ; Viral Proteins - metabolism</subject><ispartof>Molecular cell, 2002-09, Vol.10 (3), p.585-597</ispartof><rights>2002 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-bf82f3c2ef1af57b5226f99c3a1d12422a9af74646a6308bb7fc120a37b8bc0c3</citedby><cites>FETCH-LOGICAL-c491t-bf82f3c2ef1af57b5226f99c3a1d12422a9af74646a6308bb7fc120a37b8bc0c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276502006305$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12408826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chiu, Ya-Lin</creatorcontrib><creatorcontrib>Ho, C.Kiong</creatorcontrib><creatorcontrib>Saha, Nayanendu</creatorcontrib><creatorcontrib>Schwer, Beate</creatorcontrib><creatorcontrib>Shuman, Stewart</creatorcontrib><creatorcontrib>Rana, Tariq M</creatorcontrib><title>Tat Stimulates Cotranscriptional Capping of HIV mRNA</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>Here we investigated how capping and methylation of HIV pre-mRNAs are coupled to Pol II elongation. Stable binding of the capping enzyme (Mce1) and cap methyltransferase (Hcm1) to template-engaged Pol II depends on CTD phosphorylation, but not on nascent RNA. Both Mce1 and Hcm1 travel with Pol II during elongation. The capping and methylation reactions cannot occur until the nascent pre-mRNA has attained a chain length of 19–22 nucleotides. HIV pre-mRNAs are capped quantitatively when elongation complexes are halted at promoter-proximal positions, but capping is much less efficient during unimpeded Pol II elongation. Cotranscriptional capping of HIV mRNA is strongly stimulated by Tat, and this stimulation requires the C-terminal segment of Tat that mediates its direct binding to Mce1. Our findings implicate capping in an elongation checkpoint critical to HIV gene expression.</description><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression Regulation, Viral</subject><subject>Gene Products, tat - metabolism</subject><subject>HeLa Cells</subject><subject>HIV Long Terminal Repeat</subject><subject>HIV-1 - enzymology</subject><subject>HIV-1 - genetics</subject><subject>Humans</subject><subject>Methylation</subject><subject>Methyltransferases - genetics</subject><subject>Methyltransferases - metabolism</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleotidyltransferases - genetics</subject><subject>Nucleotidyltransferases - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>RNA Caps - metabolism</subject><subject>RNA Polymerase II - metabolism</subject><subject>RNA Processing, Post-Transcriptional</subject><subject>RNA, Viral - metabolism</subject><subject>tat Gene Products, Human Immunodeficiency Virus</subject><subject>Transcription, Genetic</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - metabolism</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LAzEQhoMotlZ_grIn0cNqkk2y2ZOURW2hKNjqNWSziUT2yyQr-O_dbQsee5pheGbm5QHgEsE7BBG7XyOYpTFOGb2B-BZClsCYHoHpdkwQI8f7fkQm4Mz7LwgRoTw7BROECeQcsykgGxmidbB1X8mgfZS3wcnGK2e7YNtGVlEuu842n1FrosXyI6rfXubn4MTIyuuLfZ2B96fHTb6IV6_Py3y-ihXJUIgLw7FJFNYGSUPTgmLMTJapRKJySICxzKRJCSNMDul5UaRGIQxlkha8UFAlM3C9u9u59rvXPojaeqWrSja67b1IMSOYpvAgiDhNYMJHkO5A5VrvnTaic7aW7lcgKEavYutVjNIExGLrVdBh72r_oC9qXf5v7UUOwMMO0IOPH6ud8MrqRunSOq2CKFt74MUfmWiFyw</recordid><startdate>20020901</startdate><enddate>20020901</enddate><creator>Chiu, Ya-Lin</creator><creator>Ho, C.Kiong</creator><creator>Saha, Nayanendu</creator><creator>Schwer, Beate</creator><creator>Shuman, Stewart</creator><creator>Rana, Tariq M</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>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20020901</creationdate><title>Tat Stimulates Cotranscriptional Capping of HIV mRNA</title><author>Chiu, Ya-Lin ; Ho, C.Kiong ; Saha, Nayanendu ; Schwer, Beate ; Shuman, Stewart ; Rana, Tariq M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-bf82f3c2ef1af57b5226f99c3a1d12422a9af74646a6308bb7fc120a37b8bc0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression Regulation, Viral</topic><topic>Gene Products, tat - metabolism</topic><topic>HeLa Cells</topic><topic>HIV Long Terminal Repeat</topic><topic>HIV-1 - enzymology</topic><topic>HIV-1 - genetics</topic><topic>Humans</topic><topic>Methylation</topic><topic>Methyltransferases - genetics</topic><topic>Methyltransferases - metabolism</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleotidyltransferases - genetics</topic><topic>Nucleotidyltransferases - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>RNA Caps - metabolism</topic><topic>RNA Polymerase II - metabolism</topic><topic>RNA Processing, Post-Transcriptional</topic><topic>RNA, Viral - metabolism</topic><topic>tat Gene Products, Human Immunodeficiency Virus</topic><topic>Transcription, Genetic</topic><topic>Viral Proteins - genetics</topic><topic>Viral Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chiu, Ya-Lin</creatorcontrib><creatorcontrib>Ho, C.Kiong</creatorcontrib><creatorcontrib>Saha, Nayanendu</creatorcontrib><creatorcontrib>Schwer, Beate</creatorcontrib><creatorcontrib>Shuman, Stewart</creatorcontrib><creatorcontrib>Rana, Tariq M</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>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chiu, Ya-Lin</au><au>Ho, C.Kiong</au><au>Saha, Nayanendu</au><au>Schwer, Beate</au><au>Shuman, Stewart</au><au>Rana, Tariq M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tat Stimulates Cotranscriptional Capping of HIV mRNA</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2002-09-01</date><risdate>2002</risdate><volume>10</volume><issue>3</issue><spage>585</spage><epage>597</epage><pages>585-597</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>Here we investigated how capping and methylation of HIV pre-mRNAs are coupled to Pol II elongation. Stable binding of the capping enzyme (Mce1) and cap methyltransferase (Hcm1) to template-engaged Pol II depends on CTD phosphorylation, but not on nascent RNA. Both Mce1 and Hcm1 travel with Pol II during elongation. The capping and methylation reactions cannot occur until the nascent pre-mRNA has attained a chain length of 19–22 nucleotides. HIV pre-mRNAs are capped quantitatively when elongation complexes are halted at promoter-proximal positions, but capping is much less efficient during unimpeded Pol II elongation. Cotranscriptional capping of HIV mRNA is strongly stimulated by Tat, and this stimulation requires the C-terminal segment of Tat that mediates its direct binding to Mce1. Our findings implicate capping in an elongation checkpoint critical to HIV gene expression.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12408826</pmid><doi>10.1016/S1097-2765(02)00630-5</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Expression Regulation, Viral Gene Products, tat - metabolism HeLa Cells HIV Long Terminal Repeat HIV-1 - enzymology HIV-1 - genetics Humans Methylation Methyltransferases - genetics Methyltransferases - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism Nucleic Acid Conformation Nucleotidyltransferases - genetics Nucleotidyltransferases - metabolism Promoter Regions, Genetic Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism RNA Caps - metabolism RNA Polymerase II - metabolism RNA Processing, Post-Transcriptional RNA, Viral - metabolism tat Gene Products, Human Immunodeficiency Virus Transcription, Genetic Viral Proteins - genetics Viral Proteins - metabolism |
title | Tat Stimulates Cotranscriptional Capping of HIV mRNA |
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