The SARS-CoV-2 subgenome landscape and its novel regulatory features.

Abstract

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.

• Authors: Dehe Wang, Ao Jiang, Jiangpeng Feng, Guangnan Li, Dong Guo, Muhammad Sajid, Kai Wu, Qiuhan Zhang, Yann Ponty, Sebastian Will, Feiyan Liu, Xinghai Yu, Shaopeng Li, Qianyun Liu, Xing-Lou Yang, Ming Guo, Xingqiao Li, Mingzhou Chen, Zheng-Li Shi, Ke Lan, Yu Chen, Yu Zhou
• Journal: Molecular cell (Mol Cell) Vol. 81 Issue 10 Pg. 2135-2147.e5 (05 20 2021) ISSN: 1097-4164 [Electronic] United States
• PMID: 33713597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• RNA, Viral

Topics

• Animals
• COVID-19 (genetics, metabolism)
• Caco-2 Cells
• Chlorocebus aethiops
• Genome, Viral
• High-Throughput Nucleotide Sequencing
• Humans
• RNA, Viral (genetics, metabolism)
• SARS-CoV-2 (genetics, metabolism)
• Vero Cells