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Dcp2 decapping protein modulates mRNA stability of the critical interferon regulatory factor (IRF) IRF-7.

Abstract

The mammalian Dcp2 mRNA-decapping protein functions primarily on a subset of mRNAs in a transcript-specific manner. Here we show that Dcp2 is an important modulator of genes involved in the type I interferon (IFN) response, which is the initial line of antiviral innate immune response elicited by a viral challenge. Mouse embryonic fibroblast cells with reduced Dcp2 levels (Dcp2(β/β)) contained significantly elevated levels of mRNAs encoding proteins involved in the type I IFN response. In particular, analysis of a key type I IFN transcription factor, IFN regulatory factor 7 (IRF-7), revealed an increase in both IRF-7 mRNA and protein in Dcp2(β/β) cells. Importantly, the increase in IRF-7 mRNA within the background of reduced Dcp2 levels was attributed to a stabilization of the IRF-7 mRNA, suggesting that Dcp2 normally modulates IRF-7 mRNA stability. Moreover, Dcp2 expression was also induced upon viral infection, consistent with a role in attenuating the antiviral response by promoting IRF-7 mRNA degradation. The induction of Dcp2 levels following a viral challenge and the specificity of Dcp2 in targeting the decay of IRF-7 mRNA suggest that Dcp2 may negatively contribute to the innate immune response in a negative feedback mechanism to restore normal homeostasis following viral infection.

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  • Authors

    Li Y, Dai J, Song M, Fitzgerald-Bocarsly P, Kiledjian M

    Institution

    Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.

    Source

    Molecular and cellular biology 32:6 2012 Mar pg 1164-72

    MeSH

    Animals
    Cells, Cultured
    Embryo, Mammalian
    Endoribonucleases
    Fibroblasts
    Gene Expression Regulation
    Gene Knockdown Techniques
    Genes, MHC Class II
    Host-Pathogen Interactions
    Immunity, Innate
    Interferon Regulatory Factor-7
    Lentivirus
    Lentivirus Infections
    Mice
    RNA Stability
    RNA, Messenger

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    22252322