N6-methyladenosine RNA methylation is a novel epitranscriptomic regulator of excessive alcohol drinking and vulnerability to relapse.

ABSTRACT: While internal RNA modifications have been known for decades, the contribution of epitranscriptomics to alcohol use disorder (AUD) remains unexplored. Here we investigated, for the first time, the role of the most abundant mRNA modification, N6-methyladenosine (m⁶A) in the regulation of alcohol drinking and alcohol mediated gene expression. The fat mass and obesity associated gene (FTO) plays a key role in erasing m⁶A RNA methylation marks. We generated brain m⁶A hypermethylated mice with selective deletion of FTO in neurons by crossing FTO-floxed mice (FTO-fl/fl) with the synapsin-1-CRE deleter line (Syn1-CRE). Neuronal FTO-deficient mice showed enhanced initial motivation for alcohol, achieved escalated (dependent) drinking more rapidly after repeated cyc

SUBMITTER: Maccioni R 

PROVIDER: S-EPMC12667994 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature