The role of N6-methyladenosine modification in the life cycle and disease pathogenesis of hepatitis B and C viruses

N6-methyladenosine (m 6 A) is the most prevalent modification of mammalian cellular RNAs. m 6 A methylation is linked to epigenetic regulation of several aspects of gene expression, including RNA stability, splicing, nuclear export, RNA folding, and translational activity. m 6 A modification is reversibly catalyzed by methyltransferases (m 6 A writers) and demethylases (m 6 A erasers), and the dynamics of m 6 A-modified RNA are regulated by m 6 A-binding proteins (m 6 A readers). Recently, several studies have shown that m 6 A methylation sites have been identified in hepatitis B virus (HBV) transcripts and the hepatitis C virus (HCV) RNA genome. Here, we review the role of m 6 A modification in HBV/HCV replication and its contribution to liver disease pathogenesis. A better understanding of the functions of m 6 A methylation in the life cycles of HBV and HCV is required to establish the role of these modifications in liver diseases associated with these viral infections. Hepatitis: Role of RNA modification Further investigations into the role of RNA modifications during hepatitis B and C infections could improve understanding of the hepatitis-associated liver disease. The most common RNA modification found in mammalian cells is N6-methyladenosine (m 6 A), which is linked to multiple cellular processes including gene regulation. This modification has also been identified in viral RNA, prompting Geon-Woo Kim and Aleem Siddiqui at the University of California, San Diego, USA, to review understanding of m 6 A modification during hepatitis virus infections. Depending on which part of the viral RNA is m 6 A-methylated, m 6 A modification induces complex changes in the viral life cycle. Infection with either hepatitis B or C virus also affects m 6 A modifications in host cellular RNA, influencing gene expression and inhibiting immunity. This may influence the development of liver disease and cancer during chronic hepatitis infection.