In situ structures of polymerase complex of mammalian reovirus illuminate RdRp activation and transcription regulation

文献类型： 外文期刊

第一作者： Bao, Keyan

作者： Bao, Keyan;Zhang, Xueli;Li, Dongyu;Zhu, Ping;Bao, Keyan;Zhang, Xueli;Li, Dongyu;Zhu, Ping;Sun, Wei;Sun, Zhenzhao;Wang, Jingfei

作者机构：

关键词： reovirus; cryo-em; RNA-dependent RNA polymerase; transcription

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.1； 五年影响因子：12.0 ）

ISSN： 0027-8424

年卷期： 2022 年 119 卷 50 期

页码：

收录情况： SCI

摘要： Mammalian reovirus (reovirus) is a multilayered, turreted member of Reoviridae characterized by transcription of dsRNA genome within the innermost capsid shell. Here, we present high-resolution in situ structures of reovirus transcriptase complex in an intact double-layered virion, and in the uncoated single-layered core particles in the unloaded, reloaded, pre-elongation, and elongation states, respectively, obtained by cryo-electron microscopy and sub-particle reconstructions. At the template entry of RNA-dependent RNA polymerase (RdRp), the RNA-loading region gets flexible after uncoating resulting in the unloading of terminal genomic RNA and inactivity of transcription. However, upon adding transcriptional substrates, the RNA-loading region is recovered leading the RNAs loaded again. The priming loop in RdRp was found to play a critical role in regulating transcription, which hinders the elongation of transcript in virion and triggers the rearrangement of RdRp C-terminal domain (CTD) during elongation, resulting in splitting of template-transcript hybrid and opening of transcript exit. With the integration of these structures, a transcriptional model of reovirus with five states is proposed. Our structures illuminate the RdRp activation and regulation of the multilayered turreted reovirus.

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