N6-methyladenosine modification of the 5′ epsilon structure of the HBV pregenome RNA regulates its encapsidation by the viral core protein

Abstract

Significance HBV infections are the leading cause of chronic hepatitis and carry the risk of liver cirrhosis and cancer. The HBV life cycle is perpetuated by an RNA intermediate termed pregenomic RNA (pgRNA), which is encapsidated by the viral core protein. The pgRNA packaging process is an essential step in viral replication. Here, we investigated the role of N6-methyladenosine (m 6 A) modification in the recognition of pgRNA by the core protein during encapsidation. m 6 A modification of 5′ epsilon structural motifs serves as the recognition signal for the core protein interaction, as evidenced by the failure of 5′ epsilon m 6 A mutant to encapsidate pgRNA. This study identifies the structural role of m 6 A modification in pgRNA encapsidation and provides an avenue in RNA–protein complex interactions.