N6-methyladenosine modification of HCV RNA genome regulates cap-independent IRES-mediated translation via YTHDC2 recognition
Geon‐Woo Kim, Aleem Siddiqui
Abstract
Significance N6-methyladenosine (m 6 A) modification is an emerging topic of RNA biology, and its functional roles are being investigated. m 6 A modification occurs in RNAs cotranscriptionally and regulates RNA stability and translation. m 6 A methylation has been identified in RNA virus genomes and the RNA transcripts of DNA viruses. These m 6 A modifications regulate the viral life cycle in various aspects and pathogeneses associated with individual viral infections. Here, we demonstrated that m 6 A modification of the internal ribosome entry site (IRES) region of the hepatitis C virus (HCV) recruits YTHDC2, which in concert with the cellular La antigen supports the HCV IRES-mediated translation. Our study shows the functional roles of m 6 A modification and YTHDC2 in the IRES-mediated translation.