SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:186 |
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| Enthalten in: |
Cell - 186(2023), 22 vom: 26. Okt., Seite 4834-4850.e23 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schmidt, Nora [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.10.2023 Date Revised 10.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2023.09.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Schmidt, Nora |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9 |
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| 500 | |a Date Completed 31.10.2023 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a RNA binding proteins | |
| 650 | 4 | |a RNA biology | |
| 650 | 4 | |a RNA interactome | |
| 650 | 4 | |a RNA virus | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a host factors | |
| 650 | 4 | |a omics technologies | |
| 650 | 4 | |a proteomics | |
| 650 | 4 | |a systems biology | |
| 650 | 4 | |a virus host interactions | |
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| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a SND1 protein, human |2 NLM | |
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| 700 | 1 | |a Ganskih, Sabina |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yuanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Gabel, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Zielinski, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Keshishian, Hasmik |e verfasserin |4 aut | |
| 700 | 1 | |a Lareau, Caleb A |e verfasserin |4 aut | |
| 700 | 1 | |a Zimmermann, Liv |e verfasserin |4 aut | |
| 700 | 1 | |a Makroczyova, Jana |e verfasserin |4 aut | |
| 700 | 1 | |a Pearce, Cadence |e verfasserin |4 aut | |
| 700 | 1 | |a Krey, Karsten |e verfasserin |4 aut | |
| 700 | 1 | |a Hennig, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Stegmaier, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Moyon, Lambert |e verfasserin |4 aut | |
| 700 | 1 | |a Horlacher, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Werner, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Aydin, Jens |e verfasserin |4 aut | |
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| 700 | 1 | |a Potabattula, Ramya |e verfasserin |4 aut | |
| 700 | 1 | |a Kibe, Anuja |e verfasserin |4 aut | |
| 700 | 1 | |a Dölken, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Smyth, Redmond P |e verfasserin |4 aut | |
| 700 | 1 | |a Caliskan, Neva |e verfasserin |4 aut | |
| 700 | 1 | |a Marsico, Annalisa |e verfasserin |4 aut | |
| 700 | 1 | |a Krempl, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Bodem, Jochen |e verfasserin |4 aut | |
| 700 | 1 | |a Pichlmair, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Carr, Steven A |e verfasserin |4 aut | |
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| 700 | 1 | |a Munschauer, Mathias |e verfasserin |4 aut | |
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