SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9.
RNA binding proteins
RNA biology
RNA interactome
RNA virus
SARS-CoV-2
host factors
omics technologies
proteomics
systems biology
virus host interactions
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
26 10 2023
26 10 2023
Historique:
received:
13
11
2022
revised:
13
07
2023
accepted:
01
09
2023
medline:
30
10
2023
pubmed:
5
10
2023
entrez:
5
10
2023
Statut:
ppublish
Résumé
Regulation of viral RNA biogenesis is fundamental to productive SARS-CoV-2 infection. To characterize host RNA-binding proteins (RBPs) involved in this process, we biochemically identified proteins bound to genomic and subgenomic SARS-CoV-2 RNAs. We find that the host protein SND1 binds the 5' end of negative-sense viral RNA and is required for SARS-CoV-2 RNA synthesis. SND1-depleted cells form smaller replication organelles and display diminished virus growth kinetics. We discover that NSP9, a viral RBP and direct SND1 interaction partner, is covalently linked to the 5' ends of positive- and negative-sense RNAs produced during infection. These linkages occur at replication-transcription initiation sites, consistent with NSP9 priming viral RNA synthesis. Mechanistically, SND1 remodels NSP9 occupancy and alters the covalent linkage of NSP9 to initiating nucleotides in viral RNA. Our findings implicate NSP9 in the initiation of SARS-CoV-2 RNA synthesis and unravel an unsuspected role of a cellular protein in orchestrating viral RNA production.
Identifiants
pubmed: 37794589
pii: S0092-8674(23)00980-7
doi: 10.1016/j.cell.2023.09.002
pmc: PMC10617981
pii:
doi:
Substances chimiques
Endonucleases
EC 3.1.-
RNA, Viral
0
SND1 protein, human
EC 3.1.-
nsp9 protein, SARS virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4834-4850.e23Subventions
Organisme : NHGRI NIH HHS
ID : K99 HG012579
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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