A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration.
A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration.
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DOI：
10.1016/j.chom.2016.02.007
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发表时间：
2016-03-09
影响因子：
30.3
通讯作者：
Rice CM
中科院分区：
文献类型：
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作者：
Scheel TK;Luna JM;Liniger M;Nishiuchi E;Rozen-Gagnon K;Shlomai A;Auray G;Gerber M;Fak J;Keller I;Bruggmann R;Darnell RB;Ruggli N;Rice CM
小的非编码RNA已成为病毒感染的关键调节剂。然而，除了丙型肝炎病毒需要肝脏特异性microRNA（miRNA）-122外，RNA病毒与宿主miRNA的相互作用仍然很难表征。在这里，我们使用Argonaute（AGO）蛋白的交联免疫沉淀（CLIP）来表征15种不同RNA病毒感染（包括几种临床相关病原体）背景下miRNA相互作用的强度和特异性。值得注意的是，瘟病毒的复制，对牛奶和肉类工业的主要威胁，严重依赖于细胞miR-17和let-7与病毒3 'UTR的相互作用。与典型的miRNA相互作用不同，miR-17和let-7结合增强了瘟病毒的翻译和RNA稳定性。通过瘟病毒的miR-17隔离赋予了减少的AGO结合和细胞miR-17靶标的功能性去抑制，从而改变了宿主转录组。这些发现概括了RNA病毒依赖于细胞miRNA的概念，并将病毒诱导的miRNA隔离与宿主转录组调控联系起来。
Small non-coding RNAs have emerged as key modulators of viral infection. However, with the exception of hepatitis C virus, which requires the liver-specific microRNA (miRNA)-122, the interactions of RNA viruses with host miRNAs remain poorly characterized. Here, we used crosslinking immunoprecipitation (CLIP) of the Argonaute (AGO) proteins to characterize strengths and specificities of miRNA interactions in the context of 15 different RNA virus infections, including several clinically relevant pathogens. Notably, replication of pestiviruses, a major threat to milk and meat industries, critically depended on the interaction of cellular miR-17 and let-7 with the viral 3’UTR. Unlike canonical miRNA interactions, miR-17 and let-7 binding enhanced pestivirus translation and RNA stability. miR-17 sequestration by pestiviruses conferred reduced AGO binding and functional de-repression of cellular miR-17 targets, thereby altering the host transcriptome. These findings generalize the concept of RNA virus dependence on cellular miRNAs and connect virus-induced miRNA sequestration to host transcriptome regulation.