SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9 Journal Article


Authors: Schmidt, N.; Ganskih, S.; Wei, Y.; Gabel, A.; Zielinski, S.; Keshishian, H.; Lareau, C. A.; Zimmermann, L.; Makroczyova, J.; Pearce, C.; Krey, K.; Hennig, T.; Stegmaier, S.; Moyon, L.; Horlacher, M.; Werner, S.; Aydin, J.; Olguin-Nava, M.; Potabattula, R.; Kibe, A.; Dölken, L.; Smyth, R. P.; Caliskan, N.; Marsico, A.; Krempl, C.; Bodem, J.; Pichlmair, A.; Carr, S. A.; Chlanda, P.; Erhard, F.; Munschauer, M.
Article Title: SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9
Abstract: 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. © 2023 The Author(s)
Keywords: proteomics; rna virus; systems biology; host factors; rna binding proteins; sars-cov-2; omics technologies; rna biology; rna interactome; virus host interactions
Journal Title: Cell
Volume: 186
Issue: 22
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2023-10-26
Start Page: 4834
End Page: 4850.e23
Language: English
DOI: 10.1016/j.cell.2023.09.002
PUBMED: 37794589
PROVIDER: scopus
PMCID: PMC10617981
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Caleb A Lareau
    13 Lareau