Interferon down-regulation of miR-1225-3p as an antiviral mechanism through modulating Grb2-associated binding protein 3 expression
Induction of interferons (IFNs) is a central event of antiviral innate immunity. As crucial posttranscriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimula...
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Veröffentlicht in: | The Journal of biological chemistry 2018-04, Vol.293 (16), p.5975-5986 |
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description | Induction of interferons (IFNs) is a central event of antiviral innate immunity. As crucial posttranscriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimulation, the detailed mechanisms of these miRNAs in the antiviral response are underexplored and of great significance. Here, we show that hsa-miR-1225-3p is specifically down-regulated by type I IFN through the IFN/JAK/STAT signaling pathway. Silencing endogenous miR-1225-3p inhibited infection by multiple IFN-susceptible viruses, including hepatitis C virus, Sendai virus, and Newcastle disease virus. In contrast, overexpression of miR-1225-3p impaired the antiviral effect of IFNs and facilitated viral infection. Regarding the mechanism, we identified growth factor receptor–bound protein 2–associated binding protein 3 (GAB3) as a direct target of miR-1225-3p. GAB3 expression was up-regulated by IFN, and overexpression of GAB3 demonstrated potent antiviral effects through enhancing IFN response and virus-triggered innate immune activation. Taken together, our findings reveal the biological function of miR-1225-3p for the first time and propose a novel antiviral regulation pathway in which miRNA and GAB3 participate. This study contributes to the understanding of host miRNA participation in antiviral processes of IFN. |
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As crucial posttranscriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimulation, the detailed mechanisms of these miRNAs in the antiviral response are underexplored and of great significance. Here, we show that hsa-miR-1225-3p is specifically down-regulated by type I IFN through the IFN/JAK/STAT signaling pathway. Silencing endogenous miR-1225-3p inhibited infection by multiple IFN-susceptible viruses, including hepatitis C virus, Sendai virus, and Newcastle disease virus. In contrast, overexpression of miR-1225-3p impaired the antiviral effect of IFNs and facilitated viral infection. Regarding the mechanism, we identified growth factor receptor–bound protein 2–associated binding protein 3 (GAB3) as a direct target of miR-1225-3p. GAB3 expression was up-regulated by IFN, and overexpression of GAB3 demonstrated potent antiviral effects through enhancing IFN response and virus-triggered innate immune activation. Taken together, our findings reveal the biological function of miR-1225-3p for the first time and propose a novel antiviral regulation pathway in which miRNA and GAB3 participate. This study contributes to the understanding of host miRNA participation in antiviral processes of IFN.</description><identifier>ISSN: 0021-9258</identifier><identifier>ISSN: 1083-351X</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.RA117.000738</identifier><identifier>PMID: 29496996</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - immunology ; Cell Line ; Down-Regulation - drug effects ; GAB3 ; Gene Expression Regulation - drug effects ; Growth factor receptor-bound protein 2-associated binding protein 3 ; host-pathogen interaction ; Humans ; Immunity, Innate - drug effects ; infection ; interferon ; Interferons - pharmacology ; Microbiology ; microRNA (miRNA) ; MicroRNAs - genetics ; MicroRNAs - immunology ; miR-1225–3p ; Signal Transduction - drug effects ; virus</subject><ispartof>The Journal of biological chemistry, 2018-04, Vol.293 (16), p.5975-5986</ispartof><rights>2018 © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><rights>2018 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><rights>2018 by The American Society for Biochemistry and Molecular Biology, Inc. 2018 The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-edfb845ad8437da639a515d89d86ea689c87f9a84866dc72a29e34db217daf8e3</citedby><cites>FETCH-LOGICAL-c513t-edfb845ad8437da639a515d89d86ea689c87f9a84866dc72a29e34db217daf8e3</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/PMC5912462/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912462/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29496996$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Min</creatorcontrib><creatorcontrib>Niu, Yuqiang</creatorcontrib><creatorcontrib>Fan, Jingjing</creatorcontrib><creatorcontrib>Chi, Xiaojing</creatorcontrib><creatorcontrib>Liu, Xiuying</creatorcontrib><creatorcontrib>Yang, Wei</creatorcontrib><title>Interferon down-regulation of miR-1225-3p as an antiviral mechanism through modulating Grb2-associated binding protein 3 expression</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Induction of interferons (IFNs) is a central event of antiviral innate immunity. As crucial posttranscriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimulation, the detailed mechanisms of these miRNAs in the antiviral response are underexplored and of great significance. Here, we show that hsa-miR-1225-3p is specifically down-regulated by type I IFN through the IFN/JAK/STAT signaling pathway. Silencing endogenous miR-1225-3p inhibited infection by multiple IFN-susceptible viruses, including hepatitis C virus, Sendai virus, and Newcastle disease virus. In contrast, overexpression of miR-1225-3p impaired the antiviral effect of IFNs and facilitated viral infection. Regarding the mechanism, we identified growth factor receptor–bound protein 2–associated binding protein 3 (GAB3) as a direct target of miR-1225-3p. GAB3 expression was up-regulated by IFN, and overexpression of GAB3 demonstrated potent antiviral effects through enhancing IFN response and virus-triggered innate immune activation. Taken together, our findings reveal the biological function of miR-1225-3p for the first time and propose a novel antiviral regulation pathway in which miRNA and GAB3 participate. This study contributes to the understanding of host miRNA participation in antiviral processes of IFN.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - immunology</subject><subject>Cell Line</subject><subject>Down-Regulation - drug effects</subject><subject>GAB3</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Growth factor receptor-bound protein 2-associated binding protein 3</subject><subject>host-pathogen interaction</subject><subject>Humans</subject><subject>Immunity, Innate - drug effects</subject><subject>infection</subject><subject>interferon</subject><subject>Interferons - pharmacology</subject><subject>Microbiology</subject><subject>microRNA (miRNA)</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - immunology</subject><subject>miR-1225–3p</subject><subject>Signal Transduction - drug effects</subject><subject>virus</subject><issn>0021-9258</issn><issn>1083-351X</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1rFTEUxYNY7LO6dyVZuplnPuYjcSGU0tZCQSgK7kImufNeykwyJpmnXfcfN6-vFl0UAiG5v3Nubg5C7yhZU9LVH297s745pbRbE0I6Ll6gFSWCV7yhP16iFSGMVpI14hi9Tum2MKSW9BU6ZrKWrZTtCt1f-QxxgBg8tuGXryJsllFnV85hwJO7qShjTcVnrBPWvqzsdi7qEU9gttq7NOG8jWHZbPEU7IPWb_Bl7FmlUwrG6QwW987b_f0cQwbnMcfwe46QUmn0Bh0Nekzw9nE_Qd8vzr-dfamuv15enZ1eV6ahPFdgh17Ujbai5p3VLZe6oY0V0ooWdCukEd0gtahF21rTMc0k8Nr2jBZ6EMBP0OeD77z0E1gDPpc51BzdpOOdCtqp_yvebdUm7FQjKatbVgw-PBrE8HOBlNXkkoFx1B7CkhQjlPCOULlHyQE1MaQUYXhqQ4naZ6dKduohO3XIrkje__u8J8HfsArw6QBA-aSdg6iSceANWBfBZGWDe979D0wHrEs</recordid><startdate>20180420</startdate><enddate>20180420</enddate><creator>Cheng, Min</creator><creator>Niu, Yuqiang</creator><creator>Fan, Jingjing</creator><creator>Chi, Xiaojing</creator><creator>Liu, Xiuying</creator><creator>Yang, Wei</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180420</creationdate><title>Interferon down-regulation of miR-1225-3p as an antiviral mechanism through modulating Grb2-associated binding protein 3 expression</title><author>Cheng, Min ; Niu, Yuqiang ; Fan, Jingjing ; Chi, Xiaojing ; Liu, Xiuying ; Yang, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-edfb845ad8437da639a515d89d86ea689c87f9a84866dc72a29e34db217daf8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - immunology</topic><topic>Cell Line</topic><topic>Down-Regulation - drug effects</topic><topic>GAB3</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Growth factor receptor-bound protein 2-associated binding protein 3</topic><topic>host-pathogen interaction</topic><topic>Humans</topic><topic>Immunity, Innate - drug effects</topic><topic>infection</topic><topic>interferon</topic><topic>Interferons - pharmacology</topic><topic>Microbiology</topic><topic>microRNA (miRNA)</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - immunology</topic><topic>miR-1225–3p</topic><topic>Signal Transduction - drug effects</topic><topic>virus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Min</creatorcontrib><creatorcontrib>Niu, Yuqiang</creatorcontrib><creatorcontrib>Fan, Jingjing</creatorcontrib><creatorcontrib>Chi, Xiaojing</creatorcontrib><creatorcontrib>Liu, Xiuying</creatorcontrib><creatorcontrib>Yang, Wei</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Min</au><au>Niu, Yuqiang</au><au>Fan, Jingjing</au><au>Chi, Xiaojing</au><au>Liu, Xiuying</au><au>Yang, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interferon down-regulation of miR-1225-3p as an antiviral mechanism through modulating Grb2-associated binding protein 3 expression</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2018-04-20</date><risdate>2018</risdate><volume>293</volume><issue>16</issue><spage>5975</spage><epage>5986</epage><pages>5975-5986</pages><issn>0021-9258</issn><issn>1083-351X</issn><eissn>1083-351X</eissn><abstract>Induction of interferons (IFNs) is a central event of antiviral innate immunity. As crucial posttranscriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimulation, the detailed mechanisms of these miRNAs in the antiviral response are underexplored and of great significance. Here, we show that hsa-miR-1225-3p is specifically down-regulated by type I IFN through the IFN/JAK/STAT signaling pathway. Silencing endogenous miR-1225-3p inhibited infection by multiple IFN-susceptible viruses, including hepatitis C virus, Sendai virus, and Newcastle disease virus. In contrast, overexpression of miR-1225-3p impaired the antiviral effect of IFNs and facilitated viral infection. Regarding the mechanism, we identified growth factor receptor–bound protein 2–associated binding protein 3 (GAB3) as a direct target of miR-1225-3p. GAB3 expression was up-regulated by IFN, and overexpression of GAB3 demonstrated potent antiviral effects through enhancing IFN response and virus-triggered innate immune activation. Taken together, our findings reveal the biological function of miR-1225-3p for the first time and propose a novel antiviral regulation pathway in which miRNA and GAB3 participate. This study contributes to the understanding of host miRNA participation in antiviral processes of IFN.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29496996</pmid><doi>10.1074/jbc.RA117.000738</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - immunology Cell Line Down-Regulation - drug effects GAB3 Gene Expression Regulation - drug effects Growth factor receptor-bound protein 2-associated binding protein 3 host-pathogen interaction Humans Immunity, Innate - drug effects infection interferon Interferons - pharmacology Microbiology microRNA (miRNA) MicroRNAs - genetics MicroRNAs - immunology miR-1225–3p Signal Transduction - drug effects virus |
title | Interferon down-regulation of miR-1225-3p as an antiviral mechanism through modulating Grb2-associated binding protein 3 expression |
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