The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome.

ABSTRACT: Chronic hepatitis B is a global health problem and current treatments only suppress hepatitis B virus (HBV) infection, highlighting the need for new curative treatments. Oxygen levels influence HBV replication and we previously reported that hypoxia inducible factors (HIFs) activate the basal core promoter to transcribe pre-genomic RNA. Application of a probe-enriched long-read sequencing method to map the HBV transcriptome showed an increased abundance of all viral RNAs under low oxygen or hypoxic conditions. Importantly, the hypoxic-associated increase in HBV transcripts was dependent on N6-methyladenosine (m⁶A) modifications and an m⁶A DRACH motif in the 5' stem loop of pre-genomic RNA defined transcript half-life under hypoxic conditions. Given the essential role

SUBMITTER: Tsukuda S 

PROVIDER: S-EPMC10634982 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature