tetano
Editor, Senior Moderator
Mol Cell
. 2021 Mar 3;S1097-2765(21)00166-0.
doi: 10.1016/j.molcel.2021.02.036. Online ahead of print.
The SARS-CoV-2 subgenome landscape and its novel regulatory features
Dehe Wang[SUP] 1 [/SUP], Ao Jiang[SUP] 2 [/SUP], Jiangpeng Feng[SUP] 2 [/SUP], Guangnan Li[SUP] 1 [/SUP], Dong Guo[SUP] 2 [/SUP], Muhammad Sajid[SUP] 2 [/SUP], Kai Wu[SUP] 1 [/SUP], Qiuhan Zhang[SUP] 2 [/SUP], Yann Ponty[SUP] 3 [/SUP], Sebastian Will[SUP] 3 [/SUP], Feiyan Liu[SUP] 1 [/SUP], Xinghai Yu[SUP] 1 [/SUP], Shaopeng Li[SUP] 1 [/SUP], Qianyun Liu[SUP] 2 [/SUP], Xing-Lou Yang[SUP] 4 [/SUP], Ming Guo[SUP] 2 [/SUP], Xingqiao Li[SUP] 1 [/SUP], Mingzhou Chen[SUP] 2 [/SUP], Zheng-Li Shi[SUP] 4 [/SUP], Ke Lan[SUP] 5 [/SUP], Yu Chen[SUP] 6 [/SUP], Yu Zhou[SUP] 7 [/SUP]
Affiliations
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: COVID-19; Nanopore sequencing; RNA pairing; SARS-CoV-2; biogenesis; coronavirus; sgRNA; subgenome; template switch.
. 2021 Mar 3;S1097-2765(21)00166-0.
doi: 10.1016/j.molcel.2021.02.036. Online ahead of print.
The SARS-CoV-2 subgenome landscape and its novel regulatory features
Dehe Wang[SUP] 1 [/SUP], Ao Jiang[SUP] 2 [/SUP], Jiangpeng Feng[SUP] 2 [/SUP], Guangnan Li[SUP] 1 [/SUP], Dong Guo[SUP] 2 [/SUP], Muhammad Sajid[SUP] 2 [/SUP], Kai Wu[SUP] 1 [/SUP], Qiuhan Zhang[SUP] 2 [/SUP], Yann Ponty[SUP] 3 [/SUP], Sebastian Will[SUP] 3 [/SUP], Feiyan Liu[SUP] 1 [/SUP], Xinghai Yu[SUP] 1 [/SUP], Shaopeng Li[SUP] 1 [/SUP], Qianyun Liu[SUP] 2 [/SUP], Xing-Lou Yang[SUP] 4 [/SUP], Ming Guo[SUP] 2 [/SUP], Xingqiao Li[SUP] 1 [/SUP], Mingzhou Chen[SUP] 2 [/SUP], Zheng-Li Shi[SUP] 4 [/SUP], Ke Lan[SUP] 5 [/SUP], Yu Chen[SUP] 6 [/SUP], Yu Zhou[SUP] 7 [/SUP]
Affiliations
- PMID: 33713597
- DOI: 10.1016/j.molcel.2021.02.036
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: COVID-19; Nanopore sequencing; RNA pairing; SARS-CoV-2; biogenesis; coronavirus; sgRNA; subgenome; template switch.