A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation.
A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation.
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DOI：
10.1101/gad.284604.116
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发表时间：
2016-07-15
影响因子：
10.5
通讯作者：
Cherry S
中科院分区：
文献类型：
--
作者：
Molleston JM;Sabin LR;Moy RH;Menghani SV;Rausch K;Gordesky-Gold B;Hopkins KC;Zhou R;Jensen TH;Wilusz JE;Cherry S
在这里，Molben等人发现来自病毒感染的信号将TRAMP复合物组分重新用于细胞质监视作用，其中它们选择性地接合病毒RNA进行降解以限制广泛的病毒。RNA降解受到严格调控，以选择性靶向异常RNA，包括病毒RNA，但这种调控尚未完全理解。通过在果蝇细胞中的RNAi筛选，我们鉴定了3′至5′ RNA外泌体和外泌体辅因子TRAMP（Trf 4/5-Air 1/2-Mtr 4 polyadenylation）复合物的两个组分dMtr 4和dZcchc 7，作为对抗一组RNA病毒的抗病毒剂。我们将我们的研究扩展到人类直系同源物，发现外泌体以及TRAMP组分hMTR 4和hZCCHC 7是抗病毒的。虽然hMTR 4和hZCCHC 7通常是核，但细胞质RNA病毒的感染诱导它们的输出，形成特异性识别并诱导病毒mRNA降解的细胞质复合物。此外，布尼亚病毒mRNA的3′非翻译区（UTR）足以赋予病毒诱导的外泌体降解。总之，我们的结果表明，来自病毒感染的信号将TRAMP组分重新定位为细胞质监视作用，在细胞质监视作用中，它们选择性地参与病毒RNA的降解，以限制广泛的病毒。
Here, Molleston et al. find that signals from viral infections repurpose TRAMP complex components to a cytoplasmic surveillance role where they selectively engage viral RNAs for degradation to restrict a broad range of viruses. 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.