title: 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.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.forename: Jihong
authors.initials: J
authors.lastname: Dai
authors.forename: Mangen
authors.initials: M
authors.lastname: Song
authors.forename: Patricia
authors.initials: P
authors.lastname: Fitzgerald-Bocarsly
authors.forename: Megerditch
authors.initials: M
authors.lastname: Kiledjian
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D004722:Endoribonucleases / Q000235:genetics / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005802:Genes, MHC Class II; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000235:genetics* / Q000276:immunology; D016086:Lentivirus / Q000502:physiology; D016180:Lentivirus Infections / Q000235:genetics / Q000276:immunology; D051379:Mice; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
chemical_list: D050839:Interferon Regulatory Factor-7; D012333:RNA, Messenger; C554183:Dcp2 protein, mouse; D004722:Endoribonucleases