title: Targeting of dicer-2 and RNA by a viral RNA silencing suppressor in Drosophila cells.
abstract: 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.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Qi
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Qiu
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Si
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xue
authors.initials: X
authors.lastname: Xiang
authors.forename: Jiazheng
authors.initials: J
authors.lastname: Xie
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
authors.forename: Xi
authors.initials: X
authors.lastname: Zhou
authors.forename: Yuanyang
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D030381:Nodaviridae / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D014764:Viral Proteins; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases