期刊
CELL
卷 184, 期 13, 页码 3474-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.05.033
关键词
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资金
- National Natural Science Foundation of China [U20A20135]
- National Program on Key Research Project of China [2020YFA0707500, 2017YFC0840300]
- Tsinghua University Spring Breeze Fund [2020Z99CFG015]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB37030201]
The study presents the cryo-EM structure of the SARS-CoV-2 replication-transcription complex (RTC) Cap(0)-RTC, demonstrating the proofreading mechanism of nsp14 and the role of nsp10/nsp14 in the formation of the capping complex.
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.
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