Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA.
Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA.
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DOI：
10.1038/srep27598
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发表时间：
2016-06-07
影响因子：
4.6
通讯作者：
Mizuguchi H
中科院分区：
文献类型：
--
作者：
Machitani M;Sakurai F;Wakabayashi K;Tomita K;Tachibana M;Mizuguchi H
在包括线虫和植物在内的多种生物中，RNA干扰（RNAi）是一种对抗病毒感染的防御系统;然而，目前还不清楚RNAi是否在哺乳动物细胞中起抗病毒系统的作用。相反，许多DNA病毒，包括疱疹病毒，利用转录后沉默系统来存活。在这里，我们表明Dicer通过切割Ad编码小RNA（VA-RNA）有效抑制腺病毒（Ad）的复制，所述小RNA通过抑制eIF 2 α磷酸化有效促进Ad复制为病毒microRNA（mivaRNA）。Dicer基因敲除显著增加了VA-RNA的拷贝数，导致eIF 2 α磷酸化的有效抑制和随后的Ad复制的促进。相反，Dicer的过表达显著抑制Ad复制。用mivaRNA转染不影响eIF 2 α磷酸化或Ad复制。这些结果表明Dicer介导的VA-RNA加工导致VA-RNA增强Ad复制的活性丧失，并且Dicer在哺乳动物细胞中作为针对Ad的防御系统起作用。
In various organisms, including nematodes and plants, RNA interference (RNAi) is a defense system against virus infection; however, it is unclear whether RNAi functions as an antivirus system in mammalian cells. Rather, a number of DNA viruses, including herpesviruses, utilize post-transcriptional silencing systems for their survival. Here we show that Dicer efficiently suppresses the replication of adenovirus (Ad) via cleavage of Ad-encoding small RNAs (VA-RNAs), which efficiently promote Ad replication via the inhibition of eIF2α phosphorylation, to viral microRNAs (mivaRNAs). The Dicer knockdown significantly increases the copy numbers of VA-RNAs, leading to the efficient inhibition of eIF2α phosphorylation and the subsequent promotion of Ad replication. Conversely, overexpression of Dicer significantly inhibits Ad replication. Transfection with mivaRNA does not affect eIF2α phosphorylation or Ad replication. These results indicate that Dicer-mediated processing of VA-RNAs leads to loss of activity of VA-RNAs for enhancement of Ad replication and that Dicer functions as a defence system against Ad in mammalian cells.