最近,胡远扬教授研究组发现野田村病毒亚基因RNA3是通过内部起始的方式从RNA1上生成,该文章已被病毒学的权威期刊J.Virol.在线发表。该项研究展现了一种全新的野田村病毒的亚基因起始方式,并且提供了一种理解野田村病毒复制策略的新思路。同时,关于武汉野田村病毒B2蛋白抑制RNAi的分子生物学机制的研究也已取得突破,相关论文正在投稿中。
武汉野田村病毒是胡远扬教授实验室在中国境内发现的第一株野田村病毒,这种病毒结构简单,能够在培养细胞中大量复制,并且它能穿越物种之间屏障,尤其是它的独特的基因组遗传策略使它成为研究病毒复制机制的一个很好的分子生物学模型,在生物医学方面有很好的应用前景。野田村病毒基因组包括RNA1(3.1 kb)和RNA2(1.5 kb), RNA1编码RNA依赖的RNA聚合酶 protein A,protein A不但复制基因组RNA,同时在病毒增殖过程中复制亚基因RNA3;RNA2编码衣壳蛋白前体Pro α。RNA3对于病毒复制以及病毒完整的生活周期起到了至关重要的重要。RNA3编码的B2蛋白,通过抑制RNAi,帮助病毒逃逸宿主细胞的天然免疫。另外,RNA3能够调节病毒基因组的复制。(生物谷Bioon.com)
生物谷推荐原文出处:
J. Virol. doi:10.1128/JVI.02410-10
Internal initiation is responsible for the synthesis of Wuhan Nodavirus subgenomic RNA
Yang Qiu, Dawei Cai, Nan Qi, Zhaowei Wang, Xi Zhou, Jiamin Zhang, and Yuanyang Hu*
Nodaviruses are small nonenveloped spherical viruses with a bipartite genome of RNAs. In nodaviruses, subgenomic RNA3 (sgRNA3) plays a critical role in viral replication and survival, as it coordinates the replication of two viral genomic RNAs (RNA1 and RNA2) and encodes for protein B2, which is a potent RNA-silencing inhibitor. Despite of its importance, the molecular mechanism of nodaviral sgRNA3 synthesis is still poorly understood. Here, we propose that sgRNA3 of Wuhan nodavirus (WhNV) is internally initiated from a promoter on the negative template of genomic RNA1. Serial deletion and mutation analyses further revealed that the core promoter of WhNV sgRNA3 is between positions -22 nt to +6 nt of its transcription start site. Besides, a stem-loop structure of WhNV sgRNA3 was computationally predicted upstream of sgRNA3's transcription start site. Both the secondary structure and the primary sequence were determined to be required for promoter activity. Furthermore, our results show that the synthesis of WhNV sgRNA3 is counter-regulated by the replication of WhNV genomic RNA2 which encodes a viral capsid precursor protein. And this sgRNA3 synthesis is also able to trans-activate the replication of RNA2. Altogether, findings in this study indicate that there is a newly discovered internal initiation model for the synthesis of nodaviral sgRNA.