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

Jerome M. Molleston, Leah R. Sabin, Ryan H. Moy, Sanjay V. Menghani, Keiko Rausch, Beth Gordesky-Gold, Kaycie C. Hopkins, Rui Zhou, Torben Heick Jensen, Jeremy E. Wilusz, Sara Cherry

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1658-1670
Number of pages13
JournalGenes and Development
Volume30
Issue number14
DOIs
StatePublished - Jul 15 2016
Externally publishedYes

Keywords

  • Antiviral
  • Arbovirus
  • Exosome
  • Intrinsic immunity
  • RNA degradation
  • TRAMP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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