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A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration

Publikation: Bidrag til tidsskriftTidsskriftartikel

  • Scheel, Troels Kasper Høyer
  • Joseph M Luna
  • Matthias Liniger
  • Eiko Nishiuchi
  • Kathryn Rozen-Gagnon
  • Amir Shlomai
  • Gaël Auray
  • Markus Gerber
  • John Fak
  • Irene Keller
  • Rémy Bruggmann
  • Robert B Darnell
  • Nicolas Ruggli
  • Charles M Rice
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.
OriginalsprogEngelsk
TidsskriftCell Host & Microbe
Vol/bind19
Udgave nummer3
Sider (fra-til)409-23
Antal sider15
ISSN1931-3128
DOI
StatusUdgivet - 9 mar. 2016

ID: 157961175