The SARS-CoV-2 Subgenome Landscape and its Novel Regulatory Features

Dehe Wang , Ao Jiang , Jiangpeng Feng , Guangnan Li , Dong Guo , Muhammad Sajid , Kai Wu , Qiuhan Zhang , Yann Ponty (1) , Sebastian Will (1) , 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 (2)

1 AMIBIO - Algorithms and Models for Integrative BIOlogy
2 Wuhan University [China]

COVID-19, caused by Coronavirus SARS-CoV-2, is now in global pandemic. Coronaviruses are known to generate negative subgenomes through Transcription-Regulating Sequence (TRS)-dependent template switch, but the global dynamic landscapes of coronaviral subgenomes and regulatory rules remain unclear. Here, using NGS short-read and Nanopore long-read sequencing to profile poly(A) RNAs in two cell types at multiple time points post-infection of SARS-CoV-2, we identified hundreds of template switches and constructed the dynamic landscapes of SARS-CoV-2 subgenomes. Interestingly, template switch could occur in bidirectional manner, with diverse SARS-CoV-2 subgenomes generated from successive template switching events. Majority of template switches result from RNA-RNA interactions, including seed and compensatory modes, with terminal pairing status as a key determinant. Moreover, two TRS-independent template switch modes are also responsible for subgenome biogenesis. Collectively, our findings reveal the subgenome landscape of SARS-CoV-2 and its regulatory features, providing a molecular basis for the organization and regulation of coronaviral subgenomes.

Domaines: Biologie moléculaire; Bio-informatique [q-bio.QM]

Dehe Wang, Ao Jiang, Jiangpeng Feng, Guangnan Li, Dong Guo, et al.. The SARS-CoV-2 Subgenome Landscape and its Novel Regulatory Features. Molecular Cell, In press, ⟨10.1016/j.molcel.2021.02.036⟩. ⟨hal-03154155v2⟩