Coupling of N7-methyltransferase and 3 '-5 ' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading

doi:10.1016/j.cell.2021.05.033

	Coupling of N7-methyltransferase and 3 '-5 ' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading
	Yan, Liming 1,2,3; Yang, Yunxiang 1,5; Li, Mingyu 1; Zhang, Ying 1; Zheng, Litao 2,3,4; Ge, Ji 4; Huang, Yucen C.1; Liu, Zhenyu 1; Wang, Tao1,2,3 ; Gao, Shan 1; Zhang, Ran 4; Huang, Yuanyun Y.6; Guddat, Luke W.7; Gao, Yan2,3 ; Rao, Zihe1,2,3,4,8,9,10,11 ; Lou, Zhiyong 1,11
	2021-06-24
发表期刊	CELL (IF:45.5[JCR-2023],49.0[5-Year])
ISSN	0092-8674
卷号	184 期号:13 页码:3474
发表状态	已发表
DOI	10.1016/j.cell.2021.05.033
摘要	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) ((7Me)GpppA) 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.
关键词	CRYO-EM STRUCTURE STRUCTURAL BASIS RNA-POLYMERASE HIGH-FIDELITY REPLICATION TRANSCRIPTION VIRUS NSP14 BACKTRACKING EXCISION
收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000665547300013
出版者	CELL PRESS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127664
专题	免疫化学研究所_特聘教授组_饶子和组生命科学与技术学院生命科学与技术学院_博士生
通讯作者	Gao, Yan; Rao, Zihe; Lou, Zhiyong
作者单位	1.Tsinghua Univ, Sch Med, MOE Key Lab Prot Sci, Beijing, Peoples R China; 2.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 4.Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China; 5.Tsinghua Univ, Tsinghua Univ Peking Univ Joint Ctr Life Sci, Sch Life Sci, Beijing, Peoples R China; 6.CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA; 7.Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld, Australia; 8.Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin, Peoples R China; 9.Nankai Univ, Coll Pharm, Tianjin, Peoples R China; 10.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China; 11.Guangzhou Lab, Guangzhou, Peoples R China
第一作者单位	免疫化学研究所; 生命科学与技术学院
通讯作者单位	免疫化学研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Yan, Liming,Yang, Yunxiang,Li, Mingyu,et al. Coupling of N7-methyltransferase and 3 '-5 ' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading[J]. CELL,2021,184(13):3474.
APA	Yan, Liming.,Yang, Yunxiang.,Li, Mingyu.,Zhang, Ying.,Zheng, Litao.,...&Lou, Zhiyong.(2021).Coupling of N7-methyltransferase and 3 '-5 ' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading.CELL,184(13),3474.
MLA	Yan, Liming,et al."Coupling of N7-methyltransferase and 3 '-5 ' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading".CELL 184.13(2021):3474.