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

TY - JOUR

T1 - A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation

AU - Molleston, Jerome M.

AU - Sabin, Leah R.

AU - Moy, Ryan H.

AU - Menghani, Sanjay V.

AU - Rausch, Keiko

AU - Gordesky-Gold, Beth

AU - Hopkins, Kaycie C.

AU - Zhou, Rui

AU - Jensen, Torben Heick

AU - Wilusz, Jeremy E.

AU - Cherry, Sara

PY - 2016/7/15

Y1 - 2016/7/15

N2 - 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.

AB - 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.

KW - Antiviral

KW - Arbovirus

KW - Exosome

KW - Intrinsic immunity

KW - RNA degradation

KW - TRAMP

UR - http://www.scopus.com/inward/record.url?scp=84980010333&partnerID=8YFLogxK

U2 - 10.1101/gad.284604.116

DO - 10.1101/gad.284604.116

M3 - Journal article

C2 - 27474443

AN - SCOPUS:84980010333

SN - 0890-9369

VL - 30

SP - 1658

EP - 1670

JO - Genes & Development

JF - Genes & Development

IS - 14

ER -