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Significance N6 -methyladenosine (m6 A) has recently been found to regulate numerous aspects of RNA biology. Similar to methylation of cytosine residues in DNA, eukaryotic RNA is modified by enzymatic addition of methyl groups at adenosines. m6 A modification of RNA affects a wide variety of RNA functions, including mRNA stability, translation, and in the case of viruses, viral replication and production. Our investigation revealed that the adenosine residues present in the known m6 A consensus motif within the 5′ epsilon stem loop of pregenomic RNA and the 3′ ends of all the hepatitis B virus (HBV) transcripts are m6 A modified. We demonstrate here that m6 A modification differentially modulates HBV RNA stability and reverse transcription, thereby playing two distinct regulatory roles in the HBV life cycle.

N6 -methyladenosine modification of hepatitis B virus RNA differentially regulates the viral life cycle