期刊
GENES & DEVELOPMENT
卷 30, 期 14, 页码 1658-1670出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.284604.116
关键词
RNA degradation; TRAMP; exosome; antiviral; arbovirus; intrinsic immunity
资金
- National Institute of Health [R01AI074951, U54AI057168, R01AI095500, R00GM104166, T32AI007324]
- Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease Award
- Lundbeck Foundation [R198-2015-172] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0017010] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据