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.

Links

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Publisher Full Text

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