Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b
Methylation is a prevalent posttranscriptional modification of RNAs. However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vi...
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Veröffentlicht in: | Molecular and cellular biology 2014-10, Vol.34 (19), p.3630-3641 |
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creator | Yuan, Shuai Tang, Hao Xing, Junyue Fan, Xiuqin Cai, Xiaoyu Li, Qiu Han, Pei Luo, Yuhong Zhang, Zhuojun Jiang, Bin Dou, Yali Gorospe, Myriam Wang, Wengong |
description | Methylation is a prevalent posttranscriptional modification of RNAs. However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of RISC by miR-125, thereby repressing the function of miR-125b in silencing gene expression. Our results highlight the impact of miR-125b function via methylation by NSun2. |
doi_str_mv | 10.1128/MCB.00243-14 |
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However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of RISC by miR-125, thereby repressing the function of miR-125b in silencing gene expression. Our results highlight the impact of miR-125b function via methylation by NSun2.</description><identifier>ISSN: 1098-5549</identifier><identifier>ISSN: 0270-7306</identifier><identifier>EISSN: 1098-5549</identifier><identifier>DOI: 10.1128/MCB.00243-14</identifier><identifier>PMID: 25047833</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Carboxypeptidases - metabolism ; DNA Methylation ; Epigenesis, Genetic ; Gene Silencing ; HeLa Cells ; Humans ; Hydrogen Peroxide - pharmacology ; Methyltransferases - genetics ; MicroRNAs - metabolism ; Oxidative Stress ; RNA Processing, Post-Transcriptional ; RNA, Messenger - genetics</subject><ispartof>Molecular and cellular biology, 2014-10, Vol.34 (19), p.3630-3641</ispartof><rights>Copyright © 2014, American Society for Microbiology 2014</rights><rights>Copyright © 2014, American Society for Microbiology. All Rights Reserved.</rights><rights>Copyright © 2014, American Society for Microbiology. All Rights Reserved. 2014 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-40c5f3cc8c5fdbdc986fe95753c07fd0d4c17c4ce027890c20e375d4211a37963</citedby><cites>FETCH-LOGICAL-c475t-40c5f3cc8c5fdbdc986fe95753c07fd0d4c17c4ce027890c20e375d4211a37963</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/PMC4187725/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187725/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25047833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Shuai</creatorcontrib><creatorcontrib>Tang, Hao</creatorcontrib><creatorcontrib>Xing, Junyue</creatorcontrib><creatorcontrib>Fan, Xiuqin</creatorcontrib><creatorcontrib>Cai, Xiaoyu</creatorcontrib><creatorcontrib>Li, Qiu</creatorcontrib><creatorcontrib>Han, Pei</creatorcontrib><creatorcontrib>Luo, Yuhong</creatorcontrib><creatorcontrib>Zhang, Zhuojun</creatorcontrib><creatorcontrib>Jiang, Bin</creatorcontrib><creatorcontrib>Dou, Yali</creatorcontrib><creatorcontrib>Gorospe, Myriam</creatorcontrib><creatorcontrib>Wang, Wengong</creatorcontrib><title>Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b</title><title>Molecular and cellular biology</title><addtitle>Mol Cell Biol</addtitle><description>Methylation is a prevalent posttranscriptional modification of RNAs. However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of RISC by miR-125, thereby repressing the function of miR-125b in silencing gene expression. Our results highlight the impact of miR-125b function via methylation by NSun2.</description><subject>Carboxypeptidases - metabolism</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Gene Silencing</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Methyltransferases - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Oxidative Stress</subject><subject>RNA Processing, Post-Transcriptional</subject><subject>RNA, Messenger - genetics</subject><issn>1098-5549</issn><issn>0270-7306</issn><issn>1098-5549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1LAzEQhoMotlZvniU_wK35bHYvQi22Cm2FqueQzSZ2ZZuUZFvZf-_aqlTwNAPzzDPDC8AlRn2MSXozG931ESKMJpgdgS5GWZpwzrLjg74DzmJ8RwgNMkRPQYdwxERKaRdMZqZeNpWqS-9g3sD588YRuDDrYGI0EdZLA6dma6oIlSvgeOP0DvUWzkod_GI-hJjw_BycWFVFc_Fde-B1fP8yekimT5PH0XCaaCZ4nTCkuaVap20p8kJn6cCajAtONRK2QAXTWGimDSIizZAmyFDBC0YwVlRkA9oDt3vvepOvTKGNq4Oq5DqUKxUa6VUp_05cuZRvfisZToUgvBVc7wXt8zEGY393MZJfgco2ULkLVGLW4leH937hnwRbQOyB0lkfVurDh6qQtWoqH2xQTpdR0n_Vn8lqguk</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Yuan, Shuai</creator><creator>Tang, Hao</creator><creator>Xing, Junyue</creator><creator>Fan, Xiuqin</creator><creator>Cai, Xiaoyu</creator><creator>Li, Qiu</creator><creator>Han, Pei</creator><creator>Luo, Yuhong</creator><creator>Zhang, Zhuojun</creator><creator>Jiang, Bin</creator><creator>Dou, Yali</creator><creator>Gorospe, Myriam</creator><creator>Wang, Wengong</creator><general>Taylor & Francis</general><general>American Society for Microbiology</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>5PM</scope></search><sort><creationdate>20141001</creationdate><title>Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b</title><author>Yuan, Shuai ; Tang, Hao ; Xing, Junyue ; Fan, Xiuqin ; Cai, Xiaoyu ; Li, Qiu ; Han, Pei ; Luo, Yuhong ; Zhang, Zhuojun ; Jiang, Bin ; Dou, Yali ; Gorospe, Myriam ; Wang, Wengong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-40c5f3cc8c5fdbdc986fe95753c07fd0d4c17c4ce027890c20e375d4211a37963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Carboxypeptidases - metabolism</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Gene Silencing</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Methyltransferases - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Oxidative Stress</topic><topic>RNA Processing, Post-Transcriptional</topic><topic>RNA, Messenger - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Shuai</creatorcontrib><creatorcontrib>Tang, Hao</creatorcontrib><creatorcontrib>Xing, Junyue</creatorcontrib><creatorcontrib>Fan, Xiuqin</creatorcontrib><creatorcontrib>Cai, Xiaoyu</creatorcontrib><creatorcontrib>Li, Qiu</creatorcontrib><creatorcontrib>Han, Pei</creatorcontrib><creatorcontrib>Luo, Yuhong</creatorcontrib><creatorcontrib>Zhang, Zhuojun</creatorcontrib><creatorcontrib>Jiang, Bin</creatorcontrib><creatorcontrib>Dou, Yali</creatorcontrib><creatorcontrib>Gorospe, Myriam</creatorcontrib><creatorcontrib>Wang, Wengong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular and cellular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Shuai</au><au>Tang, Hao</au><au>Xing, Junyue</au><au>Fan, Xiuqin</au><au>Cai, Xiaoyu</au><au>Li, Qiu</au><au>Han, Pei</au><au>Luo, Yuhong</au><au>Zhang, Zhuojun</au><au>Jiang, Bin</au><au>Dou, Yali</au><au>Gorospe, Myriam</au><au>Wang, Wengong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b</atitle><jtitle>Molecular and cellular biology</jtitle><addtitle>Mol Cell Biol</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>34</volume><issue>19</issue><spage>3630</spage><epage>3641</epage><pages>3630-3641</pages><issn>1098-5549</issn><issn>0270-7306</issn><eissn>1098-5549</eissn><abstract>Methylation is a prevalent posttranscriptional modification of RNAs. However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of RISC by miR-125, thereby repressing the function of miR-125b in silencing gene expression. Our results highlight the impact of miR-125b function via methylation by NSun2.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>25047833</pmid><doi>10.1128/MCB.00243-14</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Carboxypeptidases - metabolism DNA Methylation Epigenesis, Genetic Gene Silencing HeLa Cells Humans Hydrogen Peroxide - pharmacology Methyltransferases - genetics MicroRNAs - metabolism Oxidative Stress RNA Processing, Post-Transcriptional RNA, Messenger - genetics |
title | Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b |
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