Krischuns Tim, Lukarska Maria, Naffakh Nadia, Cusack Stephen
Unité Biologie des ARN et Virus Influenza, Département de Virologie, Institut Pasteur, CNRS UMR 3569, F-75015 Paris, France; email:
European Molecular Biology Laboratory, 38042 Grenoble CEDEX 9, France; email:
Annu Rev Biochem. 2021 Jun 20;90:321-348. doi: 10.1146/annurev-biochem-072820-100645. Epub 2021 Mar 26.
Influenza virus RNA-dependent RNA polymerase (FluPol) transcribes the viral RNA genome in the infected cell nucleus. In the 1970s, researchers showed that viral transcription depends on host RNA polymerase II (RNAP II) activity and subsequently that FluPol snatches capped oligomers from nascent RNAP II transcripts to prime its own transcription. Exactly how this occurs remains elusive. Here, we review recent advances in the mechanistic understanding of FluPol transcription and early events in RNAP II transcription that are relevant to cap-snatching. We describe the known direct interactions between FluPol and the RNAP II C-terminal domain and summarize the transcription-related host factors that have been found to interact with FluPol. We also discuss open questions regarding how FluPol may be targeted to actively transcribing RNAP II and the exact context and timing of cap-snatching, which is presumed to occur after cap completion but before the cap is sequestered by the nuclear cap-binding complex.
流感病毒RNA依赖的RNA聚合酶（FluPol）在被感染的细胞核中转录病毒RNA基因组。20世纪70年代，研究人员表明病毒转录依赖于宿主RNA聚合酶II（RNAP II）的活性，随后发现FluPol从新生的RNAP II转录本中抢夺带帽的寡聚体来启动自身转录。其具体发生机制仍不清楚。在此，我们综述了在FluPol转录机制理解方面的最新进展以及与帽抢夺相关的RNAP II转录早期事件。我们描述了FluPol与RNAP II C末端结构域之间已知的直接相互作用，并总结了已发现的与FluPol相互作用的转录相关宿主因子。我们还讨论了关于FluPol如何靶向活跃转录的RNAP II以及帽抢夺的确切背景和时间等悬而未决的问题，帽抢夺被认为发生在帽完成后但在帽被核帽结合复合物隔离之前。
