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首页> 外文期刊>Molecular and Cellular Biology >Dcp2 Decapping Protein Modulates mRNA Stability of the Critical Interferon Regulatory Factor (IRF) IRF-7
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Dcp2 Decapping Protein Modulates mRNA Stability of the Critical Interferon Regulatory Factor (IRF) IRF-7

机译：Dcp2开盖蛋白调节关键干扰素调节因子（IRF）IRF-7的mRNA稳定性。

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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 (Dcp2β/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 Dcp2β/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.
机译：哺乳动物Dcp2 mRNA降解蛋白主要以转录本特异性方式在mRNA的一个子集上起作用。在这里，我们显示Dcp2是参与I型干扰素（IFN）应答的基因的重要调节剂，该应答是由病毒攻击引起的抗病毒先天免疫应答的起始谱系。具有降低的Dcp2水平（Dcp2 β/β）的小鼠胚胎成纤维细胞含有显着升高的编码参与I型IFN反应的蛋白质的mRNA水平。特别是，对关键的I型IFN转录因子IFN调节因子7（IRF-7）的分析显示，Dcp2 β/β细胞中IRF-7 mRNA和蛋白均增加。重要的是，在Dcp2水平降低的背景下，IRF-7 mRNA的增加归因于IRF-7 mRNA的稳定，这表明Dcp2正常调节IRF-7 mRNA的稳定性。此外，病毒感染后还诱导了Dcp2表达，这与通过促进IRF-7 mRNA降解而减弱抗病毒反应的作用一致。病毒攻击后，Dcp2水平的诱导和靶向IRF-7 mRNA衰减的Dcp2的特异性表明，Dcp2可能以负反馈机制对先天性免疫应答起负作用，以恢复病毒感染后的正常体内平衡。

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