N6-methyladenosine Modification of Hepatitis B Virus RNA in the Coding Region of HBx .

N6-methyladenosine (m 6 A) is a post-transcriptional modification of RNA involved in transcript transport, degradation, translation, and splicing. We found that HBV RNA is modified by m 6 A predominantly in the coding region of HBx . The mutagenesis of methylation sites reduced the HBV mRNA and HBs protein levels. The suppression of m 6 A by an inhibitor or knockdown in primary hepatocytes decreased the viral RNA and HBs protein levels in the medium. These results suggest that the m 6 A modification of HBV RNA is needed for the efficient replication of HBV in hepatocytes.