The SARS-CoV-2 subgenome landscape and its novel regulatory features.
Mol Cell
; 81(10): 2135-2147.e5, 2021 05 20.
Article
in English
| MEDLINE | ID: covidwho-1117323
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA, Viral
/
Genome, Viral
/
High-Throughput Nucleotide Sequencing
/
SARS-CoV-2
/
COVID-19
Limits:
Animals
/
Humans
Language:
English
Journal:
Mol Cell
Journal subject:
Molecular Biology
Year:
2021
Document Type:
Article
Affiliation country:
J.molcel.2021.02.036
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