The m6A methylome of SARS-CoV-2 in host cells
June Liu, Yan‐Peng Xu, Kai Li, Qing Ye, Hang-Yu Zhou, Hanxiao Sun, Xiaoyu Li, Liu Yu, Yong‐Qiang Deng, Rui-Ting Li, Meng‐Li Cheng, Bo He, Jia Zhou, Xiao-Feng Li, Aiping Wu, Chengqi Yi, Cheng‐Feng Qin
Abstract
Abstract 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.