Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export
Export of messenger RNA (mRNA) from the nucleus to the cytoplasm is a critical step in the gene expression pathway of eukaryotic cells. Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA expo...
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| Veröffentlicht in: | Nucleic acids research 2012-05, Vol.40 (10), p.4562-4573 |
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| creator | Jani, Divyang Lutz, Sheila Hurt, Ed Laskey, Ronald A Stewart, Murray Wickramasinghe, Vihandha O |
| description | Export of messenger RNA (mRNA) from the nucleus to the cytoplasm is a critical step in the gene expression pathway of eukaryotic cells. Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to which ENY2, PCID2 and centrins bind and depletion of any of these components inhibits mRNA export. The crystal structure of the GANP:ENY2 complex shows that two ENY2 chains interact directly with GANP, but they have different orientations from those observed on yeast Sac3. GANP is required to recruit ENY2 to nuclear pore complexes (NPCs), but ENY2 is not necessary to recruit GANP, which requires both its CID and MCM3AP domains, together with nucleoporin Nup153. GANP and ENY2 associate with RNA polymerase II and inhibition of mRNA processing redistributes GANP from NPCs into nuclear foci indicating that mammalian TREX-2 is associated with transcription. Thus, we implicate TREX-2 as an integral component of the mammalian mRNA export machinery where it links transcription and nuclear export by facilitating the transfer of mature mRNPs from the nuclear interior to NPCs. |
| doi_str_mv | 10.1093/nar/gks059 |
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Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to which ENY2, PCID2 and centrins bind and depletion of any of these components inhibits mRNA export. The crystal structure of the GANP:ENY2 complex shows that two ENY2 chains interact directly with GANP, but they have different orientations from those observed on yeast Sac3. GANP is required to recruit ENY2 to nuclear pore complexes (NPCs), but ENY2 is not necessary to recruit GANP, which requires both its CID and MCM3AP domains, together with nucleoporin Nup153. GANP and ENY2 associate with RNA polymerase II and inhibition of mRNA processing redistributes GANP from NPCs into nuclear foci indicating that mammalian TREX-2 is associated with transcription. Thus, we implicate TREX-2 as an integral component of the mammalian mRNA export machinery where it links transcription and nuclear export by facilitating the transfer of mature mRNPs from the nuclear interior to NPCs.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gks059</identifier><identifier>PMID: 22307388</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Acetyltransferases - analysis ; Acetyltransferases - chemistry ; Acetyltransferases - metabolism ; Active Transport, Cell Nucleus ; Amino Acid Sequence ; Cell Nucleus - genetics ; Cell Nucleus - metabolism ; Crystal structure ; Crystallography, X-Ray ; Cytoplasm ; DNA-directed RNA polymerase ; Exodeoxyribonucleases - metabolism ; Gene expression ; Humans ; Intracellular Signaling Peptides and Proteins ; Models, Molecular ; Molecular Biology ; Molecular Sequence Data ; mRNA ; mRNA processing ; Nuclear Pore Complex Proteins - metabolism ; Nuclear pores ; Nuclear Proteins - analysis ; Nuclear Proteins - chemistry ; Nuclear Proteins - metabolism ; Nuclear transport ; Nucleoporins ; Phosphoproteins - metabolism ; RNA Transport ; RNA, Messenger - metabolism ; scaffolds ; Structure-function relationships ; Transcription ; Transcription Factors - chemistry ; Transcription Factors - metabolism ; Transcription, Genetic</subject><ispartof>Nucleic acids research, 2012-05, Vol.40 (10), p.4562-4573</ispartof><rights>The Author(s) 2012. 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Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to which ENY2, PCID2 and centrins bind and depletion of any of these components inhibits mRNA export. The crystal structure of the GANP:ENY2 complex shows that two ENY2 chains interact directly with GANP, but they have different orientations from those observed on yeast Sac3. GANP is required to recruit ENY2 to nuclear pore complexes (NPCs), but ENY2 is not necessary to recruit GANP, which requires both its CID and MCM3AP domains, together with nucleoporin Nup153. GANP and ENY2 associate with RNA polymerase II and inhibition of mRNA processing redistributes GANP from NPCs into nuclear foci indicating that mammalian TREX-2 is associated with transcription. Thus, we implicate TREX-2 as an integral component of the mammalian mRNA export machinery where it links transcription and nuclear export by facilitating the transfer of mature mRNPs from the nuclear interior to NPCs.</description><subject>Acetyltransferases - analysis</subject><subject>Acetyltransferases - chemistry</subject><subject>Acetyltransferases - metabolism</subject><subject>Active Transport, Cell Nucleus</subject><subject>Amino Acid Sequence</subject><subject>Cell Nucleus - genetics</subject><subject>Cell Nucleus - metabolism</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Cytoplasm</subject><subject>DNA-directed RNA polymerase</subject><subject>Exodeoxyribonucleases - metabolism</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Models, Molecular</subject><subject>Molecular Biology</subject><subject>Molecular Sequence Data</subject><subject>mRNA</subject><subject>mRNA processing</subject><subject>Nuclear Pore Complex Proteins - metabolism</subject><subject>Nuclear pores</subject><subject>Nuclear Proteins - analysis</subject><subject>Nuclear Proteins - chemistry</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nuclear transport</subject><subject>Nucleoporins</subject><subject>Phosphoproteins - metabolism</subject><subject>RNA Transport</subject><subject>RNA, Messenger - metabolism</subject><subject>scaffolds</subject><subject>Structure-function relationships</subject><subject>Transcription</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFrFTEUhYNY7LO68QdIliJMm5tM3mQ2QimtCsVCqeAu5OXdeS82k4xJplb3_m_Tvlp05-pyud89nMMh5BWwQ2C9OAomHW2uM5P9E7IAseRN2y_5U7JggskGWKv2yfOcvzIGLcj2GdnnXLBOKLUgv87mYIuLwXhqwprmkmZb5lRXuzXJ2ILJ_TR3BI0DLVukoxlH450J9Ory9EvDqY3j5PG2Hk2h3oXrTEsyIdvkpvvH765saZitR5PoiDlj2GCil5-OKd5OMZUXZG8wPuPLh3lAPp-dXp18aM4v3n88OT5vbAtQaiwlFAfsFfSrJQx83SqrLEiJnHHBBfZoV1wMrZKglBArYbHrsAdkppNMHJB3O91pXo24thiqUa-n5EaTfuhonP73EtxWb-KNFqJTqpdV4M2DQIrfZsxFjy5b9N4EjHPWwDhTkgvg_4GC7GRbA1X07Q61KeaccHh0BEzfVaxrxXpXcYVf_53hEf3TqfgN4ialUw</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Jani, Divyang</creator><creator>Lutz, Sheila</creator><creator>Hurt, Ed</creator><creator>Laskey, Ronald A</creator><creator>Stewart, Murray</creator><creator>Wickramasinghe, Vihandha O</creator><general>Oxford University Press</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>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20120501</creationdate><title>Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export</title><author>Jani, Divyang ; Lutz, Sheila ; Hurt, Ed ; Laskey, Ronald A ; Stewart, Murray ; Wickramasinghe, Vihandha O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-4983821e9819b61f2d48c8c155e202323e9ecb23f48518833b3ce77e91e0a7503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acetyltransferases - analysis</topic><topic>Acetyltransferases - chemistry</topic><topic>Acetyltransferases - metabolism</topic><topic>Active Transport, Cell Nucleus</topic><topic>Amino Acid Sequence</topic><topic>Cell Nucleus - genetics</topic><topic>Cell Nucleus - metabolism</topic><topic>Crystal structure</topic><topic>Crystallography, X-Ray</topic><topic>Cytoplasm</topic><topic>DNA-directed RNA polymerase</topic><topic>Exodeoxyribonucleases - metabolism</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Models, Molecular</topic><topic>Molecular Biology</topic><topic>Molecular Sequence Data</topic><topic>mRNA</topic><topic>mRNA processing</topic><topic>Nuclear Pore Complex Proteins - metabolism</topic><topic>Nuclear pores</topic><topic>Nuclear Proteins - analysis</topic><topic>Nuclear Proteins - chemistry</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nuclear transport</topic><topic>Nucleoporins</topic><topic>Phosphoproteins - metabolism</topic><topic>RNA Transport</topic><topic>RNA, Messenger - metabolism</topic><topic>scaffolds</topic><topic>Structure-function relationships</topic><topic>Transcription</topic><topic>Transcription Factors - chemistry</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jani, Divyang</creatorcontrib><creatorcontrib>Lutz, Sheila</creatorcontrib><creatorcontrib>Hurt, Ed</creatorcontrib><creatorcontrib>Laskey, Ronald A</creatorcontrib><creatorcontrib>Stewart, Murray</creatorcontrib><creatorcontrib>Wickramasinghe, Vihandha O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jani, Divyang</au><au>Lutz, Sheila</au><au>Hurt, Ed</au><au>Laskey, Ronald A</au><au>Stewart, Murray</au><au>Wickramasinghe, Vihandha O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2012-05-01</date><risdate>2012</risdate><volume>40</volume><issue>10</issue><spage>4562</spage><epage>4573</epage><pages>4562-4573</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>Export of messenger RNA (mRNA) from the nucleus to the cytoplasm is a critical step in the gene expression pathway of eukaryotic cells. Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to which ENY2, PCID2 and centrins bind and depletion of any of these components inhibits mRNA export. The crystal structure of the GANP:ENY2 complex shows that two ENY2 chains interact directly with GANP, but they have different orientations from those observed on yeast Sac3. GANP is required to recruit ENY2 to nuclear pore complexes (NPCs), but ENY2 is not necessary to recruit GANP, which requires both its CID and MCM3AP domains, together with nucleoporin Nup153. GANP and ENY2 associate with RNA polymerase II and inhibition of mRNA processing redistributes GANP from NPCs into nuclear foci indicating that mammalian TREX-2 is associated with transcription. Thus, we implicate TREX-2 as an integral component of the mammalian mRNA export machinery where it links transcription and nuclear export by facilitating the transfer of mature mRNPs from the nuclear interior to NPCs.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>22307388</pmid><doi>10.1093/nar/gks059</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetyltransferases - analysis Acetyltransferases - chemistry Acetyltransferases - metabolism Active Transport, Cell Nucleus Amino Acid Sequence Cell Nucleus - genetics Cell Nucleus - metabolism Crystal structure Crystallography, X-Ray Cytoplasm DNA-directed RNA polymerase Exodeoxyribonucleases - metabolism Gene expression Humans Intracellular Signaling Peptides and Proteins Models, Molecular Molecular Biology Molecular Sequence Data mRNA mRNA processing Nuclear Pore Complex Proteins - metabolism Nuclear pores Nuclear Proteins - analysis Nuclear Proteins - chemistry Nuclear Proteins - metabolism Nuclear transport Nucleoporins Phosphoproteins - metabolism RNA Transport RNA, Messenger - metabolism scaffolds Structure-function relationships Transcription Transcription Factors - chemistry Transcription Factors - metabolism Transcription, Genetic |
| title | Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export |
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