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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/7690| The mechanism of RNA capping by SARS-CoV-2 | |
| Gina Park Adam Osinski Genaro Hernandez Jennifer Eitson Abir Majumdar Marco Tonelli Katherine Henzler_Wildman Krzysztof Pawłowski zhe chen Yang Li John Schoggins Vincent Tagliabracci | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2022.02.07.479471 | |
| https://www.biorxiv.org/content/10.1101/2022.02.07.479471v1 | |
| The SARS-CoV-2 RNA genome contains a 5′-cap that facilitates translation of viral proteins, protection from exonucleases and evasion of the host immune response. How this cap is made is not completely understood. Here, we reconstitute the SARS-CoV-2 7MeGpppA2′-O-Me-RNA cap using virally encoded non-structural proteins (nsps). We show that the kinase-like NiRAN domain of nsp12 transfers RNA to the amino terminus of nsp9, forming a covalent RNA-protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers RNA to GDP, forming the cap core structure GpppA-RNA. The nsp14 and nsp16 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication-transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system that the N-terminus of nsp9 and the kinase-like active site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19. | |
| medRxiv and bioRxiv | |
| 09-02-2022 | |
| Preimpreso | |
| https://www.biorxiv.org/ | |
| Inglés | |
| Epidemia COVID-19 | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Versión publicada | |
| publishedVersion - Versión publicada | |
| Aparece en las colecciones: | Artículos científicos |
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| The mechanism of RNA capping by SARS COV2.pdf | 7.37 MB | Adobe PDF | Visualizar/Abrir |