Resumen
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.
Idioma original | English |
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Páginas (desde-hasta) | 3474-3485.e11 |
Publicación | Cell |
Volumen | 184 |
N.º | 13 |
DOI | |
Estado | Published - jun. 24 2021 |
Publicado de forma externa | Sí |
Nota bibliográfica
Funding Information:This work was supported by the National Natural Science Foundation of China ( U20A20135 ), the National Program on Key Research Project of China ( 2020YFA0707500 and 2017YFC0840300 ), Tsinghua University Spring Breeze Fund ( 2020Z99CFG015 ), and the Strategic Priority Research Program of the Chinese Academy of Sciences ( XDB37030201 ).
Publisher Copyright:
© 2021 Elsevier Inc.
ASJC Scopus Subject Areas
- General Biochemistry,Genetics and Molecular Biology
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't