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.
【저자키워드】 RNA modification, Mechanisms of disease, 【초록키워드】 SARS-CoV-2, Mutation, SARS-COV-2 infection, Genome, molecular mechanism, coronavirus 2, RNA, Spread, Epidemic, Phylogenetic analysis, cells, Cluster, experiment, respiratory, Methylation, Interaction, Analysis, regulate, mRNAs, genomic RNA, strain, health emergency, high mortality, motif, Host, Combined, identify, indicated, functional, unique, increase in, triggered, exhibiting, miCLIP, 【제목키워드】 SARS-CoV-2, host cell,