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Targeting of Dicer-2 and RNA by a Viral RNA Silencing Suppressor in Drosophila Cells

SprMorn 添加于 2012/5/21 13:25:25  976次阅读 | 0次推荐 | 0个评论

RNA interference (RNAi) is a eukaryotic gene-silencing mechanism that functions in antiviral immunity in diverse organisms. To combat RNAi-mediated immunity, viruses encode viral suppressors of RNA silencing (VSRs) that target RNA and protein components in the RNAi machinery. Although the endonuclease Dicer plays key roles in RNAi immunity, little is known about how VSRs target Dicer. Here, we show that the B2 protein from Wuhan nodavirus (WhNV), the counterpart of Flock House virus (FHV), suppresses Drosophila melanogaster RNAi by directly interacting with Dicer-2 (Dcr-2) and sequestering double-stranded RNA (dsRNA) and small interfering RNA (siRNA). Further investigations reveal that WhNV B2 binds to the RNase III and Piwi-Argonaut-Zwille (PAZ) domains of Dcr-2 via its C-terminal region, thereby blocking the activities of Dcr-2 in processing dsRNA and incorporating siRNA into the RNA-induced silencing complex (RISC). Moreover, we uncover an interrelationship among diverse activities of WhNV B2, showing that RNA binding enhances the B2–Dcr-2 interaction by promoting B2 homodimerization. Taken together, our findings establish a model of suppression of Drosophila RNAi by WhNV B2 targeting both Dcr-2 and RNA and provide evidence that an interrelationship exists among diverse activities of VSRs to antagonize RNAi.

作 者:Nan Qia, Lei Zhanga, Yang Qiua, Zhaowei Wanga, Jie Sia, Yongxiang Liua, Xue Xianga, Jiazheng Xiea, Cheng-Feng Qinb, Xi Zhoua and Yuanyang Hua
期刊名称: jv
期卷页: 第卷 第期 页
学科领域:生命科学 » 微生物学 » 病毒学
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原文链接:http://intl-jvi.asm.org/content/86/10/5763.abstract
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相关报道: http://paper.sciencenet.cn/htmlpaper/201252113281975924107.shtm
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