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首页> 外文期刊>Biochemistry >Regulation of Influenza RNA Polymerase Activity and the Switch between Replication and Transcription by the Concentrations of the vRNA 5 ' End, the Cap Source, and the Polymerase
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Regulation of Influenza RNA Polymerase Activity and the Switch between Replication and Transcription by the Concentrations of the vRNA 5 ' End, the Cap Source, and the Polymerase

机译：调节流感RNA聚合酶活性以及通过vRNA 5'末端，帽来源和聚合酶浓度控制复制和转录之间的转换

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摘要

The influenza RNA-dependent RNA polymerase (RdRp) both replicates the flu's RNA genome and transcribes its mRNA. Replication occurs de novo; however, initiation of transcription requires a 7-methylguanosine 5'-capped primer that is "snatched" from host mRNA via endonuclease and cap binding functions of the influenza polymerase. A key question is how the virus regulates the relative amounts of transcription and replication. We found that the concentration of a capped cellular mRNA, the concentration of the 5' end of the viral RNA, and the concentration of RdRp all regulate the relative amounts of replication versus transcription. The host mRNA, from which the RdRp snatches its capped primer, acts to upregulate transcription and repress replication. Elevated concentrations of the RdRp itself switch the influenza polymerase toward replication, likely through an oligomerization of the polymerase. The 5' end of the vRNA template both activates replication and inhibits transcription of the vRNA template, thereby indicating that RdRp contains an allosteric binding site for the 5' end of the vRNA template. These data provide insights into the regulation of RdRp throughout the viral life cycle and how it synthesizes the appropriate amounts of viral mRNA and replication products (vRNA and cRNA).
机译：依赖于流感RNA的RNA聚合酶（RdRp）可以复制流感的RNA基因组并转录其mRNA。复制从头开始;但是，转录的起始需要通过流感病毒聚合酶的核酸内切酶和帽结合功能从宿主mRNA中“捕获”的7-甲基鸟苷5'帽引物。一个关键问题是病毒如何调节转录和复制的相对量。我们发现加帽的细胞mRNA的浓度，病毒RNA的5'端的浓度和RdRp的浓度均调节复制相对于转录的相对量。 RdRp捕获其帽状引物的宿主mRNA可上调转录并抑制复制。升高的RdRp本身的浓度可能会使流感病毒聚合酶转向复制，这很可能是通过聚合酶的低聚作用来实现的。 vRNA模板的5'端既激活复制又抑制vRNA模板的转录，从而表明RdRp包含vRNA模板的5'端的变构结合位点。这些数据提供了对整个病毒生命周期中RdRp调控的见解，以及它如何合成适量的病毒mRNA和复制产物（vRNA和cRNA）。

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