The Significance of N6-Methyladenosine RNA Methylation in Regulating the Hepatitis B Virus Life Cycle

J Microbiol Biotechnol. 2024 Feb 28;34(2):233-239. doi: 10.4014/jmb.2309.09013. Epub 2023 Oct 31.


N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferaselike (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

Keywords: HBV chronic infection; HBV life cycle; Hepatitis B virus; N6-methyladenosine RNA methylation; hepatocellular carcinoma; innate immunity.

Publication types

  • Review

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Hepatitis B virus* / genetics
  • Humans
  • Liver Diseases*
  • Methylation
  • RNA
  • RNA Methylation


  • RNA
  • FTO protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO