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A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation

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  • Jerome M. Molleston, The Pennsylvania State University
  • ,
  • Leah R. Sabin, The Pennsylvania State University
  • ,
  • Ryan H. Moy, The Pennsylvania State University
  • ,
  • Sanjay V. Menghani, The Pennsylvania State University
  • ,
  • Keiko Rausch, The Pennsylvania State University
  • ,
  • Beth Gordesky-Gold, The Pennsylvania State University
  • ,
  • Kaycie C. Hopkins, The Pennsylvania State University
  • ,
  • Rui Zhou, Sanford-Burnham Medical Research Institute
  • ,
  • Torben Heick Jensen
  • Jeremy E. Wilusz, The Pennsylvania State University
  • ,
  • Sara Cherry, The Pennsylvania State University

RNA degradation is tightly regulated to selectively target aberrant RNAs, including viral RNA, but this regulation is incompletely understood. Through RNAi screening in Drosophila cells, we identified the 3’-to-5’ RNA exosome and two components of the exosome cofactor TRAMP (Trf4/5-Air1/2-Mtr4 polyadenylation) complex, dMtr4 and dZcchc7, as antiviral against a panel of RNA viruses. We extended our studies to human orthologs and found that the exosome as well as TRAMP components hMTR4 and hZCCHC7 are antiviral. While hMTR4 and hZCCHC7 are normally nuclear, infection by cytoplasmic RNA viruses induces their export, forming a cytoplasmic complex that specifically recognizes and induces degradation of viral mRNAs. Furthermore, the 3′ untranslated region (UTR) of bunyaviral mRNA is sufficient to confer virus-induced exosomal degradation. Altogether, our results reveal that signals from viral infection repurpose TRAMP components to a cytoplasmic surveillance role where they selectively engage viral RNAs for degradation to restrict a broad range of viruses.

OriginalsprogEngelsk
TidsskriftGenes & Development
Vol/bind30
Nummer14
Sider (fra-til)1658-1670
Antal sider13
ISSN0890-9369
DOI
StatusUdgivet - 15 jul. 2016

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