MicroRNA-939 restricts Hepatitis B virus by targeting Jmjd3-mediated and C/EBPα-coordinated chromatin remodeling
Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investiga...
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| Veröffentlicht in: | Scientific reports 2016-10, Vol.6 (1), p.35974-35974, Article 35974 |
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| creator | Chen, Cuncun Wu, Min Zhang, Wen Lu, Wei Zhang, Min Zhang, Zhanqing Zhang, Xiaonan Yuan, Zhenghong |
| description | Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect. Jmjd3 appeared to enhance the transcription efficiency of HBV enhancer II/core promoter (En II) in a C/EBPα-dependent manner. However, the demethylase activity of Jmjd3 was not required in this process. Rather, Jmjd3’s transactivation activity depended on its interaction with C/EBPα. This coordinated action further recruited the Brm containing SWI/SNF chromatin remodeling complex which promoted the transcription of HBV RNAs. Taken together, we propose that the miR-939-Jmjd3 axis perturbs the accessibility of En II promoter to essential nuclear factors (C/EBPα and SWI/SNF complex) therefore leading to compromised viral RNA synthesis and hence restricted viral multiplication. |
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Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect. Jmjd3 appeared to enhance the transcription efficiency of HBV enhancer II/core promoter (En II) in a C/EBPα-dependent manner. However, the demethylase activity of Jmjd3 was not required in this process. Rather, Jmjd3’s transactivation activity depended on its interaction with C/EBPα. This coordinated action further recruited the Brm containing SWI/SNF chromatin remodeling complex which promoted the transcription of HBV RNAs. Taken together, we propose that the miR-939-Jmjd3 axis perturbs the accessibility of En II promoter to essential nuclear factors (C/EBPα and SWI/SNF complex) therefore leading to compromised viral RNA synthesis and hence restricted viral multiplication.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep35974</identifier><identifier>PMID: 27779233</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/109 ; 13/89 ; 38/15 ; 38/61 ; 631/326/596/1550 ; 692/699/255/234/2513/1549 ; CCAAT-Enhancer-Binding Protein-alpha - metabolism ; Cell Line ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone - metabolism ; Hepatitis B virus - immunology ; Hepatitis B virus - physiology ; Hepatocytes - virology ; Host-Pathogen Interactions ; Humanities and Social Sciences ; Humans ; Jumonji Domain-Containing Histone Demethylases - metabolism ; MicroRNAs - metabolism ; multidisciplinary ; Promoter Regions, Genetic ; Protein Binding ; RNA, Viral - biosynthesis ; Science ; Transcription Factors - metabolism ; Virus Replication</subject><ispartof>Scientific reports, 2016-10, Vol.6 (1), p.35974-35974, Article 35974</ispartof><rights>The Author(s) 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-bdb83edd8757b2d3ac25a91ed3387b374a5b1cc464b914947340767e2c04ae6b3</citedby><cites>FETCH-LOGICAL-c410t-bdb83edd8757b2d3ac25a91ed3387b374a5b1cc464b914947340767e2c04ae6b3</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/PMC5078794/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078794/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27779233$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Cuncun</creatorcontrib><creatorcontrib>Wu, Min</creatorcontrib><creatorcontrib>Zhang, Wen</creatorcontrib><creatorcontrib>Lu, Wei</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><creatorcontrib>Zhang, Zhanqing</creatorcontrib><creatorcontrib>Zhang, Xiaonan</creatorcontrib><creatorcontrib>Yuan, Zhenghong</creatorcontrib><title>MicroRNA-939 restricts Hepatitis B virus by targeting Jmjd3-mediated and C/EBPα-coordinated chromatin remodeling</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect. Jmjd3 appeared to enhance the transcription efficiency of HBV enhancer II/core promoter (En II) in a C/EBPα-dependent manner. However, the demethylase activity of Jmjd3 was not required in this process. Rather, Jmjd3’s transactivation activity depended on its interaction with C/EBPα. This coordinated action further recruited the Brm containing SWI/SNF chromatin remodeling complex which promoted the transcription of HBV RNAs. Taken together, we propose that the miR-939-Jmjd3 axis perturbs the accessibility of En II promoter to essential nuclear factors (C/EBPα and SWI/SNF complex) therefore leading to compromised viral RNA synthesis and hence restricted viral multiplication.</description><subject>13/109</subject><subject>13/89</subject><subject>38/15</subject><subject>38/61</subject><subject>631/326/596/1550</subject><subject>692/699/255/234/2513/1549</subject><subject>CCAAT-Enhancer-Binding Protein-alpha - metabolism</subject><subject>Cell Line</subject><subject>Chromatin Assembly and Disassembly</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>Hepatitis B virus - immunology</subject><subject>Hepatitis B virus - physiology</subject><subject>Hepatocytes - virology</subject><subject>Host-Pathogen Interactions</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Jumonji Domain-Containing Histone Demethylases - metabolism</subject><subject>MicroRNAs - metabolism</subject><subject>multidisciplinary</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>RNA, Viral - biosynthesis</subject><subject>Science</subject><subject>Transcription Factors - metabolism</subject><subject>Virus Replication</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNptkdtKXDEUhkOpVFEvfAHJpRV2zXGyc1PQwWrFHij1OuTkmGHvZEyyBR-rL-IzmXbsYKG5Scj68mWxfgAOMPqAEe1PSvYryqVgb8AOQYx3hBLy9tV5G-yXskRtcSIZlu_ANhFCSELpDrj_EmxOP76edpJKmH2pOdha4KVf6RpqKPAMPoQ8FWgeYdV54WuIC3g1Lh3tRu-Crt5BHR2cn5yffX_61dmUsgvxz729y2lsntjMY3J-aG_3wNatHorff9l3wc2n85_zy-7628Xn-el1ZxlGtTPO9NQ71wsuDHFUW8K1xN5R2gtDBdPcYGvZjBmJmWSCMiRmwhOLmPYzQ3fBx7V3NZnWqPWxZj2oVQ6jzo8q6aD-rcRwpxbpQXEkeiFZExy9CHK6n9pk1BiK9cOgo09TUbinnFOOpGjo-zXaZllaILebbzBSv1NSm5Qae_i6rw35N5MGHK-B0kpx4bNapinHNqv_2J4BJE-dvg</recordid><startdate>20161025</startdate><enddate>20161025</enddate><creator>Chen, Cuncun</creator><creator>Wu, Min</creator><creator>Zhang, Wen</creator><creator>Lu, Wei</creator><creator>Zhang, Min</creator><creator>Zhang, Zhanqing</creator><creator>Zhang, Xiaonan</creator><creator>Yuan, Zhenghong</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161025</creationdate><title>MicroRNA-939 restricts Hepatitis B virus by targeting Jmjd3-mediated and C/EBPα-coordinated chromatin remodeling</title><author>Chen, Cuncun ; Wu, Min ; Zhang, Wen ; Lu, Wei ; Zhang, Min ; Zhang, Zhanqing ; Zhang, Xiaonan ; Yuan, Zhenghong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-bdb83edd8757b2d3ac25a91ed3387b374a5b1cc464b914947340767e2c04ae6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13/109</topic><topic>13/89</topic><topic>38/15</topic><topic>38/61</topic><topic>631/326/596/1550</topic><topic>692/699/255/234/2513/1549</topic><topic>CCAAT-Enhancer-Binding Protein-alpha - metabolism</topic><topic>Cell Line</topic><topic>Chromatin Assembly and Disassembly</topic><topic>Chromosomal Proteins, Non-Histone - metabolism</topic><topic>Hepatitis B virus - immunology</topic><topic>Hepatitis B virus - physiology</topic><topic>Hepatocytes - virology</topic><topic>Host-Pathogen Interactions</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Jumonji Domain-Containing Histone Demethylases - metabolism</topic><topic>MicroRNAs - metabolism</topic><topic>multidisciplinary</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding</topic><topic>RNA, Viral - biosynthesis</topic><topic>Science</topic><topic>Transcription Factors - metabolism</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Cuncun</creatorcontrib><creatorcontrib>Wu, Min</creatorcontrib><creatorcontrib>Zhang, Wen</creatorcontrib><creatorcontrib>Lu, Wei</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><creatorcontrib>Zhang, Zhanqing</creatorcontrib><creatorcontrib>Zhang, Xiaonan</creatorcontrib><creatorcontrib>Yuan, Zhenghong</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Cuncun</au><au>Wu, Min</au><au>Zhang, Wen</au><au>Lu, Wei</au><au>Zhang, Min</au><au>Zhang, Zhanqing</au><au>Zhang, Xiaonan</au><au>Yuan, Zhenghong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-939 restricts Hepatitis B virus by targeting Jmjd3-mediated and C/EBPα-coordinated chromatin remodeling</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-10-25</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>35974</spage><epage>35974</epage><pages>35974-35974</pages><artnum>35974</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect. Jmjd3 appeared to enhance the transcription efficiency of HBV enhancer II/core promoter (En II) in a C/EBPα-dependent manner. However, the demethylase activity of Jmjd3 was not required in this process. Rather, Jmjd3’s transactivation activity depended on its interaction with C/EBPα. This coordinated action further recruited the Brm containing SWI/SNF chromatin remodeling complex which promoted the transcription of HBV RNAs. Taken together, we propose that the miR-939-Jmjd3 axis perturbs the accessibility of En II promoter to essential nuclear factors (C/EBPα and SWI/SNF complex) therefore leading to compromised viral RNA synthesis and hence restricted viral multiplication.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27779233</pmid><doi>10.1038/srep35974</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/109 13/89 38/15 38/61 631/326/596/1550 692/699/255/234/2513/1549 CCAAT-Enhancer-Binding Protein-alpha - metabolism Cell Line Chromatin Assembly and Disassembly Chromosomal Proteins, Non-Histone - metabolism Hepatitis B virus - immunology Hepatitis B virus - physiology Hepatocytes - virology Host-Pathogen Interactions Humanities and Social Sciences Humans Jumonji Domain-Containing Histone Demethylases - metabolism MicroRNAs - metabolism multidisciplinary Promoter Regions, Genetic Protein Binding RNA, Viral - biosynthesis Science Transcription Factors - metabolism Virus Replication |
| title | MicroRNA-939 restricts Hepatitis B virus by targeting Jmjd3-mediated and C/EBPα-coordinated chromatin remodeling |
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