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Fig. 3.

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Fig. 3. The role of m6A modification in regulating the HBV life cycle. In the context of the HBV life cycle, the HBV HBx protein plays a pivotal role in orchestrating m6A modification. Initially, HBx interacts with METTL3/14 in the cytosol, facilitating their subsequent nuclear import. During HBV transcription, HBx guides METTL3/14 to the HBV cccDNA, where they co-transcriptionally introduce m6A methylation into HBV transcripts. This m6A methylation occurs at a consensus m6A motif located within the lower stem of HBV epsilon structure. HBV pgRNA contains two of these motifs at its 5' and 3' termini due to terminal redundancy, whereas other viral transcripts have only one motif, typically in the 3' terminal sequence. Notably, the HBV 5' terminal m6A modification promotes the interaction with the core protein by affecting the region surrounding the priming site for reverse transcription initiation. This interaction, in turn, promotes the reverse transcription of HBV DNA from pgRNA. Conversely, the HBV 3' terminal m6A modification, present in all viral RNAs, decreases RNA stability by interacting with YTHDF2. Additionally, the reader proteins YTHDC1 and FMRP induce m6A methylation of HBV mRNA, subsequently enhancing translation. This intricate interplay of m6A modification mechanisms significantly impacts the regulation of the HBV life cycle.
J. Microbiol. Biotechnol. 2024;34:233~239 https://doi.org/10.4014/jmb.2309.09013
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