FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2
Mutations in the RNA-binding protein FUS (fused in sarcoma)/TLS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the normal role of FUS is incompletely understood. We found that FUS binds the C-terminal domain (CTD) of RNA polymerase II (RNAP2) and prev...
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| Veröffentlicht in: | Genes & development 2012-12, Vol.26 (24), p.2690-2695 |
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| container_title | Genes & development |
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| creator | Schwartz, Jacob C Ebmeier, Christopher C Podell, Elaine R Heimiller, Joseph Taatjes, Dylan J Cech, Thomas R |
| description | Mutations in the RNA-binding protein FUS (fused in sarcoma)/TLS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the normal role of FUS is incompletely understood. We found that FUS binds the C-terminal domain (CTD) of RNA polymerase II (RNAP2) and prevents inappropriate hyperphosphorylation of Ser2 in the RNAP2 CTD at thousands of human genes. The loss of FUS leads to RNAP2 accumulation at the transcription start site and a shift in mRNA isoform expression toward early polyadenylation sites. Thus, in addition to its role in alternative RNA splicing, FUS has a general function in orchestrating CTD phosphorylation during RNAP2 transcription. |
| doi_str_mv | 10.1101/gad.204602.112 |
| format | Article |
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We found that FUS binds the C-terminal domain (CTD) of RNA polymerase II (RNAP2) and prevents inappropriate hyperphosphorylation of Ser2 in the RNAP2 CTD at thousands of human genes. The loss of FUS leads to RNAP2 accumulation at the transcription start site and a shift in mRNA isoform expression toward early polyadenylation sites. Thus, in addition to its role in alternative RNA splicing, FUS has a general function in orchestrating CTD phosphorylation during RNAP2 transcription.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.204602.112</identifier><identifier>PMID: 23249733</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Cell Line ; Gene Expression Regulation ; HEK293 Cells ; HeLa Cells ; Humans ; Immunoglobulin G - metabolism ; Phosphorylation ; Protein Binding ; Protein Structure, Tertiary ; Research Communication ; RNA Polymerase II - metabolism ; RNA-Binding Protein FUS - metabolism ; Serine - metabolism ; Transcription Initiation Site ; Transcription, Genetic - physiology</subject><ispartof>Genes & development, 2012-12, Vol.26 (24), p.2690-2695</ispartof><rights>Copyright © 2012 by Cold Spring Harbor Laboratory Press 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-6a1408023291768ad9fcc3835d2026bece9134883589e56f2d526b208dd5e1e23</citedby><cites>FETCH-LOGICAL-c456t-6a1408023291768ad9fcc3835d2026bece9134883589e56f2d526b208dd5e1e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533074/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533074/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23249733$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schwartz, Jacob C</creatorcontrib><creatorcontrib>Ebmeier, Christopher C</creatorcontrib><creatorcontrib>Podell, Elaine R</creatorcontrib><creatorcontrib>Heimiller, Joseph</creatorcontrib><creatorcontrib>Taatjes, Dylan J</creatorcontrib><creatorcontrib>Cech, Thomas R</creatorcontrib><title>FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Mutations in the RNA-binding protein FUS (fused in sarcoma)/TLS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the normal role of FUS is incompletely understood. 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Thus, in addition to its role in alternative RNA splicing, FUS has a general function in orchestrating CTD phosphorylation during RNAP2 transcription.</description><subject>Cell Line</subject><subject>Gene Expression Regulation</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Immunoglobulin G - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>Research Communication</subject><subject>RNA Polymerase II - metabolism</subject><subject>RNA-Binding Protein FUS - metabolism</subject><subject>Serine - metabolism</subject><subject>Transcription Initiation Site</subject><subject>Transcription, Genetic - physiology</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1Lw0AQXUSx9ePqUfboJXU_kk32IpRqtVBUbHtettlJG0mydTcR-u_d0lr0MAzz5vHmMQ-hG0oGlBJ6v9JmwEgsCAszO0F9msQySuI0PUV9kkkSSS5kD114_0kIEUSIc9RjnMUy5byP3seLGV6WjfG4XQMezR-xLfDH6xBvbLWtwWkPeDLBujHYwaqrdAsel63Hm7X1odw2QKVtsG7xDBy7QmeFrjxcH_olWoyf5qOXaPr2PBkNp1EeJ6KNhKYxyUgwImkqMm1kkec844lhhIkl5CApj7MAZBISUTCTBJiRzJgEKDB-iR72uptuWYPJoWmdrtTGlbV2W2V1qf5vmnKtVvZb8YRzksZB4O4g4OxXB75VdelzqCrdgO28oizlTITP7qiDPTV31nsHxfEMJWoXgwoxqH0MYd6Zu_1r7kj__Tv_AbM6ggQ</recordid><startdate>20121215</startdate><enddate>20121215</enddate><creator>Schwartz, Jacob C</creator><creator>Ebmeier, Christopher C</creator><creator>Podell, Elaine R</creator><creator>Heimiller, Joseph</creator><creator>Taatjes, Dylan J</creator><creator>Cech, Thomas R</creator><general>Cold Spring Harbor Laboratory 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>5PM</scope></search><sort><creationdate>20121215</creationdate><title>FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2</title><author>Schwartz, Jacob C ; Ebmeier, Christopher C ; Podell, Elaine R ; Heimiller, Joseph ; Taatjes, Dylan J ; Cech, Thomas R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-6a1408023291768ad9fcc3835d2026bece9134883589e56f2d526b208dd5e1e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Cell Line</topic><topic>Gene Expression Regulation</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Immunoglobulin G - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>Research Communication</topic><topic>RNA Polymerase II - metabolism</topic><topic>RNA-Binding Protein FUS - metabolism</topic><topic>Serine - metabolism</topic><topic>Transcription Initiation Site</topic><topic>Transcription, Genetic - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schwartz, Jacob C</creatorcontrib><creatorcontrib>Ebmeier, Christopher C</creatorcontrib><creatorcontrib>Podell, Elaine R</creatorcontrib><creatorcontrib>Heimiller, Joseph</creatorcontrib><creatorcontrib>Taatjes, Dylan J</creatorcontrib><creatorcontrib>Cech, Thomas R</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>PubMed Central (Full Participant titles)</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schwartz, Jacob C</au><au>Ebmeier, Christopher C</au><au>Podell, Elaine R</au><au>Heimiller, Joseph</au><au>Taatjes, Dylan J</au><au>Cech, Thomas R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>2012-12-15</date><risdate>2012</risdate><volume>26</volume><issue>24</issue><spage>2690</spage><epage>2695</epage><pages>2690-2695</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><abstract>Mutations in the RNA-binding protein FUS (fused in sarcoma)/TLS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the normal role of FUS is incompletely understood. 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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Cell Line Gene Expression Regulation HEK293 Cells HeLa Cells Humans Immunoglobulin G - metabolism Phosphorylation Protein Binding Protein Structure, Tertiary Research Communication RNA Polymerase II - metabolism RNA-Binding Protein FUS - metabolism Serine - metabolism Transcription Initiation Site Transcription, Genetic - physiology |
| title | FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2 |
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