Drosha as an interferon-independent antiviral factor
Drosha as an interferon-independent antiviral factor
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DOI：
10.1073/pnas.1319635111
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发表时间：
2014-05-13
影响因子：
11.1
通讯作者：
Tenoever, Benjamin R.
中科院分区：
文献类型：
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作者：
Shapiro, Jillian S.;Schmid, Sonja;Tenoever, Benjamin R.
抗病毒小干扰RNA的利用被认为主要限于植物、线虫和节肢动物。为了确定宿主小RNA机制和哺乳动物对病毒感染的细胞反应之间是否存在生理相互作用，我们评估了在存在和不存在Dicer或Drosha（负责产生小RNA的RNase III核酸酶）的情况下的抗病毒活性。尽管Dicer的缺失并不影响细胞对病毒感染的反应，但Drosha缺失导致病毒水平显著增加。在这里，我们表明，不同的RNA病毒触发输出蛋白1（XPO 1/CRM 1）依赖Drosha易位到细胞质中的方式独立的从头蛋白质合成或典型的I型IFN系统。此外，在不存在Drosha的情况下增加的病毒感染不是由于病毒小RNA的丢失，而是与病毒基因组RNA的切割和宿主转录组的调节相关。综上所述，我们认为Drosha代表了用于对抗病毒感染的细胞防御的一个独特而保守的分支。
Utilization of antiviral small interfering RNAs is thought to be largely restricted to plants, nematodes, and arthropods. In an effort to determine whether a physiological interplay exists between the host small RNA machinery and the cellular response to virus infection in mammals, we evaluated antiviral activity in the presence and absence of Dicer or Drosha, the RNase III nucleases responsible for generating small RNAs. Although loss of Dicer did not compromise the cellular response to virus infection, Drosha deletion resulted in a significant increase in virus levels. Here, we demonstrate that diverse RNA viruses trigger exportin 1 (XPO1/CRM1)-dependent Drosha translocation into the cytoplasm in a manner independent of de novo protein synthesis or the canonical type I IFN system. Additionally, increased virus infection in the absence of Drosha was not due to a loss of viral small RNAs but, instead, correlated with cleavage of viral genomic RNA and modulation of the host transcriptome. Taken together, we propose that Drosha represents a unique and conserved arm of the cellular defenses used to combat virus infection.