ABSTRACT The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing global public crisis. Although viral RNA modification has been reported based on the transcriptome architecture, the types and functions of RNA modification are still unknown. In this study, we evaluated the roles of RNA N6-methyladenosine (m 6 A) modification in SARS-CoV-2. Our methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and Nanopore direct RNA sequencing (DRS) analysis showed that SARS-CoV-2 RNA contained m 6 A modification. Moreover, SARS-CoV-2 infection not only increased the expression of methyltransferase-like 3 (METTL3) but also altered its distribution. Modification of METTL3 expression by short hairpin RNA or plasmid transfection for knockdown or overexpression, respectively, affected viral replication. Furthermore, the viral key protein RdRp interacted with METTL3, and METTL3 was distributed in both the nucleus and cytoplasm in the presence of RdRp. RdRp appeared to modulate the sumoylation and ubiquitination of METTL3 via an unknown mechanism. Taken together, our findings demonstrated that the host m 6 A modification complex interacted with viral proteins to modulate SARS-CoV-2 replication.
【저자키워드】 viral replication, N6-methyladenosine, methyltransferase-like 3, respiratory syndrome coronavirus-2, 【초록키워드】 coronavirus disease, Transcriptome, RNA modification, SARS-CoV-2, pandemic, SARS-COV-2 infection, Sequencing, Direct RNA sequencing, RNA, Protein, RdRP, SARS-CoV-2 RNA, Viral RNA, distribution, expression, SARS-CoV-2 replication, mechanism, function, Coronavirus-2, Analysis, METTL3, cytoplasm, acute respiratory syndrome, Viral protein, complex, knockdown, overexpression, immunoprecipitation, nucleus, Modification, Host, affected, caused, reported, evaluated, modulate, demonstrated, methylated RNA, plasmid transfection, 【제목키워드】 RNA, respiratory,