title: A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation.
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.
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Molleston
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Leah R
authors.initials: LR
authors.lastname: Sabin
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Ryan H
authors.initials: RH
authors.lastname: Moy
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Sanjay V
authors.initials: SV
authors.lastname: Menghani
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Keiko
authors.initials: K
authors.lastname: Rausch
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Beth
authors.initials: B
authors.lastname: Gordesky-Gold
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Kaycie C
authors.initials: KC
authors.lastname: Hopkins
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA;
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark;
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Wilusz
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
mesh_terms: D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000821:virology; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics; D026723:Polyadenylation; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D020871:RNA Stability / Q000502:physiology*; D012327:RNA Virus Infections / Q000378:metabolism / Q000821:virology; D012328:RNA Viruses / Q000502:physiology; D012367:RNA, Viral / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D012367:RNA, Viral; D014157:Transcription Factors
keywords: RNA degradation; TRAMP; antiviral; arbovirus; exosome; intrinsic immunity