德国马普生物物理化学研究所Patrick Cramer、维尔茨堡大学Utz Fischer等研究人员合作解析了痘病毒转录的结构基础。相关论文于2019年12月12日发表在《细胞》杂志上。

研究人员以转录延伸复合物的形式以及包含病毒加帽酶（CE）的共转录加帽复合物的形式报道了牛痘病毒编码的多亚基RNA聚合酶（vRNAP）的冷冻电镜（cryo-EM）结构。三功能CE形成两个可移动模块，可结合RNA出口通道周围的聚合酶表面。RNA从vRNAP活性位点穿过此通道延伸到CE三磷酸酶的活性位点。结构比较表明，从转录起始到RNA封端和延伸的过渡过程中，不断增长的RNA会触发转录机制表面上的大规模重排。 这一结构揭示了痘病毒RNA合成和共转录修饰的基础。

据了解，痘病毒使用vRNAP和RNA加工因子在宿主细胞质中产生m7G戴帽的mRNA。

附：英文原文

Title: Structural Basis of Poxvirus Transcription: Transcribing and Capping Vaccinia Complexes

Author: Hauke S. Hillen, Julia Bartuli, Clemens Grimm, Christian Dienemann, Kristina Bedenk, Aladar A. Szalay, Utz Fischer, Patrick Cramer

Issue&Volume: 2019/12/12

Abstract: Poxviruses use virus-encoded multisubunit RNA polymerases (vRNAPs) and RNA-processing factors to generate m 7G-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.

DOI: 10.1016/j.cell.2019.11.023

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31280-2