Article

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

Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.
Molecular and cellular biology (impact factor: 6.06). 03/2012; 32(6):1164-72. DOI:10.1128/MCB.06328-11 pp.1164-72
Source: PubMed

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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    A B Shyu, M E Greenberg, J G Belasco
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    ABSTRACT: Rapid degradation of c-fos proto-oncogene mRNA is crucial for transient c-fos gene expression. Experiments were performed to investigate the cellular mechanisms responsible for the extremely short half-life of human c-fos mRNA in growth-factor-stimulated fibroblasts. These experiments demonstrate the existence of two distinct cellular pathways for rapid c-fos mRNA degradation. Each of these pathways recognizes a different, functionally independent instability determinant within the c-fos transcript. One instability determinant, which is located within the c-fos 3'-untranslated region, is a 75-nucleotide AU-rich segment. Insertion of this element into beta-globin mRNA markedly reduces the half-life of that normally long-lived message. Nevertheless, specific deletion of the AU-rich element from c-fos mRNA has little effect on the transcript's cytoplasmic half-life due to the presence of the other c-fos instability determinant, which is located in the protein-coding segment of the c-fos message. Examination of mRNA decay in cells treated with transcription inhibitors indicates that one c-fos mRNA degradation pathway is dependent on RNA synthesis, whereas the other is not.
    Genes & Development 02/1989; 3(1):60-72. · 11.66 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

antiviral innate immune response elicited
 
antiviral response
 
Dcp2 expression
 
Dcp2 levels
 
genes
 
IFN regulatory factor 7
 
induction
 
initial line
 
innate immune response
 
IRF-7 mRNA
 
IRF-7 mRNA degradation
 
key type
 
mammalian Dcp2 mRNA-decapping protein functions
 
Mouse embryonic fibroblast cells
 
mRNAs encoding proteins
 
negative feedback mechanism
 
normal homeostasis
 
stabilization
 
viral challenge
 
viral infection