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Coupling of N7-methyltransferase and 3'-5' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading.
Yan, Liming; Yang, Yunxiang; Li, Mingyu; Zhang, Ying; Zheng, Litao; Ge, Ji; Huang, Yucen C; Liu, Zhenyu; Wang, Tao; Gao, Shan; Zhang, Ran; Huang, Yuanyun Y; Guddat, Luke W; Gao, Yan; Rao, Zihe; Lou, Zhiyong.
  • Yan L; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Yang Y; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • Li M; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China.
  • Zhang Y; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China.
  • Zheng L; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; School of Life Sciences, Tsinghua University, Beijing, China.
  • Ge J; School of Life Sciences, Tsinghua University, Beijing, China.
  • Huang YC; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China.
  • Liu Z; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China.
  • Wang T; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Gao S; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China.
  • Zhang R; School of Life Sciences, Tsinghua University, Beijing, China.
  • Huang YY; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Guddat LW; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
  • Gao Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China. Electronic address: yan-gao13@mails.tsinghua.edu.cn.
  • Rao Z; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; School of Life Sciences, Tsinghua University, Beijing, China; St
  • Lou Z; MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; Guangzhou Laboratory, Guangzhou, China. Electronic address: louzy@mail.tsinghua.edu.cn.
Cell ; 184(13): 3474-3485.e11, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1240208
ABSTRACT
The capping of mRNA and the proofreading play essential roles in SARS-CoV-2 replication and transcription. Here, we present the cryo-EM structure of the SARS-CoV-2 replication-transcription complex (RTC) in a form identified as Cap(0)-RTC, which couples a co-transcriptional capping complex (CCC) composed of nsp12 NiRAN, nsp9, the bifunctional nsp14 possessing an N-terminal exoribonuclease (ExoN) and a C-terminal N7-methyltransferase (N7-MTase), and nsp10 as a cofactor of nsp14. Nsp9 and nsp12 NiRAN recruit nsp10/nsp14 into the Cap(0)-RTC, forming the N7-CCC to yield cap(0) (7MeGpppA) at 5' end of pre-mRNA. A dimeric form of Cap(0)-RTC observed by cryo-EM suggests an in trans backtracking mechanism for nsp14 ExoN to facilitate proofreading of the RNA in concert with polymerase nsp12. These results not only provide a structural basis for understanding co-transcriptional modification of SARS-CoV-2 mRNA but also shed light on how replication fidelity in SARS-CoV-2 is maintained.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Exoribonucleases / Coronavirus RNA-Dependent RNA Polymerase / SARS-CoV-2 / Methyltransferases Limits: Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.05.033

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Exoribonucleases / Coronavirus RNA-Dependent RNA Polymerase / SARS-CoV-2 / Methyltransferases Limits: Humans Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.05.033