Structural Basis of Poxvirus Transcription: Transcribing and Capping Vaccinia Complexes
Structural Basis of Poxvirus Transcription: Transcribing and Capping Vaccinia Complexes
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DOI：
10.1016/j.cell.2019.11.023
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发表时间：
2019-12-12
期刊：
影响因子：
64.5
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
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作者：
Hillen, Hauke S.;Bartuli, Julia;Cramer, Patrick
痘病毒使用病毒编码的多亚基RNA聚合酶（vRNAP）和RNA加工因子在宿主细胞质中产生m（7）G-帽mRNA。在随附的论文中，我们报道了原型牛痘病毒的核心和完整vRNAP复合物的结构（Grimm等人，2019;在这个问题上的细胞）。在这里，我们提出的冷冻电子显微镜（cryo-EM）结构的牛痘vRNAP的形式的转录延伸复合物和形式的共转录帽复合物，包含病毒的加帽酶（CE）。三功能CE形成两个移动的模块，其结合RNA出口通道周围的聚合酶表面。RNA从vRNAP活性位点延伸通过该通道并进入CE三磷酸酶的活性位点。结构比较表明，不断增长的RNA触发大规模的重排过程中，从转录起始到RNA帽和延伸的转录机器的表面上。我们的结构揭示了痘病毒RNA合成和共转录修饰的基础。
Poxviruses use virus-encoded multisubunit RNA polymerases (vRNAPs) and RNA-processing factors to generate m(7)G-capped mRNAs in the host cytoplasm. In the accompanying paper, we report structures of core and complete vRNAP complexes of the prototypic Vaccinia poxvirus (Grimm et al., 2019; in this issue of Cell). Here, we present the cryo-electron microscopy (cryo-EM) structures of Vaccinia vRNAP in the form of a transcribing elongation complex and in the form of a co-transcriptional capping complex that contains the viral capping enzyme (CE). The trifunctional CE forms two mobile modules that bind the polymerase surface around the RNA exit tunnel. RNA extends from the vRNAP active site through this tunnel and into the active site of the CE triphosphatase. Structural comparisons suggest that growing RNA triggers large-scale rearrangements on the surface of the transcription machinery during the transition from transcription initiation to RNA capping and elongation. Our structures unravel the basis for synthesis and co-transcriptional modification of poxvirus RNA.