当前位置: X-MOL 学术Mol. Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The SARS-CoV-2 subgenome landscape and its novel regulatory features
Molecular Cell ( IF 16.0 ) Pub Date : 2021-03-03 , DOI: 10.1016/j.molcel.2021.02.036
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

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.



中文翻译:

SARS-CoV-2亚基因组格局及其新颖的调控功能

由严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)引起的冠状病毒病2019(COVID-19)目前是全球性大流行。已知CoV通过依赖转录调节序列(TRS)的模板转换产生阴性亚基因组(亚基因组RNA [sgRNAs]),但冠状病毒亚基因组的全球动态格局和调节规则仍不清楚。在这里,使用SARS-CoV-2感染后多个时间点在两种细胞类型中使用下一代测序(NGS)短读和纳米孔长读poly(A)RNA测序,我们鉴定了数百个模板开关并构建了SARS-CoV-2亚基因组的动态景观。有趣的是,模板切换可以双向发生,具有从连续的模板切换事件中产生的各种SARS-CoV-2亚基因组。大多数模板转换来自RNA-RNA相互作用,包括种子和补偿模式,而末端配对状态是关键决定因素。两种不依赖TRS的模板切换模式也负责亚基因组的生物发生。我们的发现揭示了SARS-CoV-2的亚基因组格局及其调控特征,为理解亚基因组生物发生和开发新的抗病毒策略提供了分子基础。

更新日期:2021-03-03
down
wechat
bug