Chan Annie Y, Vreede Frank T, Smith Matt, Engelhardt Othmar G, Fodor Ervin
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Virology. 2006 Jul 20;351(1):210-7. doi: 10.1016/j.virol.2006.03.005. Epub 2006 Apr 19.
The influenza virus RNA-dependent RNA polymerase interacts with the serine-5 phosphorylated carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II). It was proposed that this interaction allows the viral RNA polymerase to gain access to host mRNA-derived capped RNA fragments required as primers for the initiation of viral mRNA synthesis. Here, we show, using a chromatin immunoprecipitation (ChIP) analysis, that similar amounts of Pol II associate with Pol II promoter DNAs in influenza virus-infected and mock-infected cells. However, there is a statistically significant reduction in Pol II densities in the coding region of Pol II genes in infected cells. Thus, influenza virus specifically interferes with Pol II elongation, but not Pol II initiation. We propose that influenza virus RNA polymerase, by binding to the CTD of initiating Pol II and subsequent cleavage of the capped 5' end of the nascent transcript, triggers premature Pol II termination.
流感病毒RNA依赖性RNA聚合酶与RNA聚合酶II（Pol II）大亚基的丝氨酸5磷酸化羧基末端结构域（CTD）相互作用。有人提出，这种相互作用使病毒RNA聚合酶能够获取宿主mRNA衍生的带帽RNA片段，这些片段是启动病毒mRNA合成所需的引物。在此，我们通过染色质免疫沉淀（ChIP）分析表明，在流感病毒感染的细胞和模拟感染的细胞中，与Pol II启动子DNA结合的Pol II数量相似。然而，在感染细胞中，Pol II基因编码区域的Pol II密度有统计学上的显著降低。因此，流感病毒特异性干扰Pol II延伸，但不干扰Pol II起始。我们提出，流感病毒RNA聚合酶通过结合起始Pol II的CTD并随后切割新生转录本的带帽5'末端，触发Pol II过早终止。
