The SARS-CoV-2 subgenome landscape and its novel regulatory features
Copyright © 2021 Elsevier Inc. All rights reserved..
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global pandemic. CoVs are known to generate negative subgenomes (subgenomic RNAs [sgRNAs]) through transcription-regulating sequence (TRS)-dependent template switching, but the global dynamic landscapes of coronaviral subgenomes and regulatory rules remain unclear. Here, using next-generation sequencing (NGS) short-read and Nanopore long-read poly(A) RNA sequencing in two cell types at multiple time points after infection with SARS-CoV-2, we identified hundreds of template switches and constructed the dynamic landscapes of SARS-CoV-2 subgenomes. Interestingly, template switching could occur in a bidirectional manner, with diverse SARS-CoV-2 subgenomes generated from successive template-switching events. The majority of template switches result from RNA-RNA interactions, including seed and compensatory modes, with terminal pairing status as a key determinant. Two TRS-independent template switch modes are also responsible for subgenome biogenesis. Our findings reveal the subgenome landscape of SARS-CoV-2 and its regulatory features, providing a molecular basis for understanding subgenome biogenesis and developing novel anti-viral strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:81 |
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| Enthalten in: |
Molecular cell - 81(2021), 10 vom: 20. Mai, Seite 2135-2147.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Dehe [VerfasserIn] |
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| Links: |
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| Themen: |
Biogenesis |
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| Anmerkungen: |
Date Completed 31.05.2021 Date Revised 31.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.molcel.2021.02.036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Wang, Dehe |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The SARS-CoV-2 subgenome landscape and its novel regulatory features |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 31.05.2021 | ||
| 500 | |a Date Revised 31.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global pandemic. CoVs are known to generate negative subgenomes (subgenomic RNAs [sgRNAs]) through transcription-regulating sequence (TRS)-dependent template switching, but the global dynamic landscapes of coronaviral subgenomes and regulatory rules remain unclear. Here, using next-generation sequencing (NGS) short-read and Nanopore long-read poly(A) RNA sequencing in two cell types at multiple time points after infection with SARS-CoV-2, we identified hundreds of template switches and constructed the dynamic landscapes of SARS-CoV-2 subgenomes. Interestingly, template switching could occur in a bidirectional manner, with diverse SARS-CoV-2 subgenomes generated from successive template-switching events. The majority of template switches result from RNA-RNA interactions, including seed and compensatory modes, with terminal pairing status as a key determinant. Two TRS-independent template switch modes are also responsible for subgenome biogenesis. Our findings reveal the subgenome landscape of SARS-CoV-2 and its regulatory features, providing a molecular basis for understanding subgenome biogenesis and developing novel anti-viral strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Nanopore sequencing | |
| 650 | 4 | |a RNA pairing | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a biogenesis | |
| 650 | 4 | |a coronavirus | |
| 650 | 4 | |a sgRNA | |
| 650 | 4 | |a subgenome | |
| 650 | 4 | |a template switch | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 700 | 1 | |a Jiang, Ao |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Jiangpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guangnan |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Sajid, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qiuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Ponty, Yann |e verfasserin |4 aut | |
| 700 | 1 | |a Will, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Feiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xinghai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shaopeng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qianyun |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xing-Lou |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xingqiao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Mingzhou |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Zheng-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Lan, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yu |e verfasserin |4 aut | |
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