Targeting of dicer-2 and RNA by a viral RNA silencing suppressor in Drosophila cells
Autor: | Yang Qiu, Jiazheng Xie, Jie Si, Xi Zhou, Lei Zhang, Yuanyang Hu, Zhaowei Wang, Xue Xiang, Yongxiang Liu, Nan Qi, Cheng-Feng Qin |
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Rok vydání: | 2012 |
Předmět: |
Ribonuclease III
Small interfering RNA RNA-induced transcriptional silencing RNA-induced silencing complex Immunology Trans-acting siRNA Biology Microbiology Cell Line Small hairpin RNA Viral Proteins RNA interference Virology Animals Drosophila Proteins Nodaviridae RNA Small Interfering Genetics fungi RNA silencing Insect Science biology.protein Pathogenesis and Immunity Drosophila RNA Interference RNA Helicases Dicer Protein Binding |
Zdroj: | Journal of virology. 86(10) |
ISSN: | 1098-5514 |
Popis: | 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. |
Databáze: | OpenAIRE |
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