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
Hauptverfasser: Cheng, Min, Niu, Yuqiang, Fan, Jingjing, Chi, Xiaojing, Liu, Xiuying, Yang, Wei
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container_end_page 5986
container_issue 16
container_start_page 5975
container_title The Journal of biological chemistry
container_volume 293
creator Cheng, Min
Niu, Yuqiang
Fan, Jingjing
Chi, Xiaojing
Liu, Xiuying
Yang, Wei
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. 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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. 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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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