The m6A methylome of SARS-CoV-2 in host cells

• Published in: Cell research Vol. 31; no. 4; pp. 404 - 414
• Main Authors: Liu, Jun’e, Xu, Yan-Peng, Li, Kai, Ye, Qing, Zhou, Hang-Yu, Sun, Hanxiao, Li, Xiaoyu, Yu, Liu, Deng, Yong-Qiang, Li, Rui-Ting, Cheng, Meng-Li, He, Bo, Zhou, Jia, Li, Xiao-Feng, Wu, Aiping, Yi, Chengqi, Qin, Cheng-Feng
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-04-2021; Nature Publishing Group
• Subjects: 14/32; 45/90; 45/91; 631/337/1645/2570; 631/80/304; Biomedical and Life Sciences; Cell Biology; Coronaviruses; COVID-19; Genomics; Global health; Life Sciences; Localization; Methylation; Mutation; N6-methyladenosine; Phylogeny; Public health; Respiratory diseases; Ribonucleic acid; RNA; Severe acute respiratory syndrome coronavirus 2; Viral diseases
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/s41422-020-00465-7

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency because of its rapid spread and high mortality. The molecular mechanism of interaction between host and viral genomic RNA is yet unclear. We demonstrate herein that SARS-CoV-2 genomic RNA, as well as the negative-sense RNA, is dynamically
N
6
-methyladenosine (m
6
A)-modified in human and monkey cells. Combined RIP-seq and miCLIP analyses identified a total of 8 m
6
A sites at single-base resolution in the genome. Especially, epidemic strains with mutations at these identified m
6
A sites have emerged worldwide, and formed a unique cluster in the US as indicated by phylogenetic analysis. Further functional experiments showed that m
6
A methylation negatively regulates SARS-CoV-2 infection. SARS-CoV-2 infection also triggered a global increase in host m
6
A methylome, exhibiting altered localization and motifs of m
6
A methylation in mRNAs. Altogether, our results identify m
6
A as a dynamic epitranscriptomic mark mediating the virus–host interaction.