Proteomic and phylogenetic coevolution analyses of pM79 and pM92 identify interactions with RNA polymerase II and delineate the murine cytomegalovirus late transcription complex
Proteomic and phylogenetic coevolution analyses of pM79 and pM92 identify interactions with RNA polymerase II and delineate the murine cytomegalovirus late transcription complex
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DOI：
10.1099/jgv.0.000676
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发表时间：
2017-02-01
影响因子：
3.8
通讯作者：
French, Anthony R.
中科院分区：
文献类型：
--
作者：
Chapa, Travis J.;Du, Yushen;French, Anthony R.
乙型疱疹病毒晚期病毒基因表达的调控在很大程度上是不明确的。我们之前已经证明，小鼠巨细胞病毒蛋白pM79和pM92是晚期基因转录所必需的。在这里，我们通过确定pM79和pM92在感染过程中的相互作用伙伴来深入了解pM79和pM92活性的机制。免疫共沉淀耦合质谱研究表明，pM79和pM92与一系列参与转录的细胞和病毒蛋白相互作用。具体来说，我们确定RNA聚合酶II是pM79和pM92的细胞靶标。我们使用蛋白间协同进化分析来展示pM79和pM92如何可能组装成由晚期转录调控因子pM49、pM87和pM95组成的晚期转录复合体。将蛋白质组学方法与协同进化计算分析相结合，为pM79、pM92和RNA聚合酶II之间的关系提供了新的见解，并允许生成调节晚期基因转录的多组分病毒复合物模型。
The regulation of the late viral gene expression in betaherpesviruses is largely undefined. We have previously shown that the murine cytomegalovirus proteins pM79 and pM92 are required for late gene transcription. Here, we provide insight into the mechanism of pM79 and pM92 activity by determining their interaction partners during infection. Co-immunoprecipitation-coupled MS studies demonstrate that pM79 and pM92 interact with an array of cellular and viral proteins involved in transcription. Specifically, we identify RNA polymerase II as a cellular target for both pM79 and pM92. We use inter-protein coevolution analysis to show how pM79 and pM92 likely assemble into a late transcription complex composed of late transcription regulators pM49, pM87 and pM95. Combining proteomic methods with coevolution computational analysis provides novel insights into the relationship between pM79, pM92 and RNA polymerase II and allows the generation of a model of the multi-component viral complex that regulates late gene transcription.