METTL4 regulates synaptic UCP2 N6-adenosine methylation to mediate pain hypersensitivity in female mice.

ABSTRACT: Epitranscriptomics modifications play an important role in sex-dependent biological phenomena. N6-adenosine methylation (m6A), the most prevalent epitranscriptomics modification in eukaryotic mRNA, participates in regulating various sex-specific physiological processes. Here, we generated METTL4 knockout mice lacking methyltransferase-like 4, which mediates m6A. Behavioral analyses revealed that only female METTL4^-/- mice exhibited pain hypersensitivity, with subsequent experiments showing the involvement of METTL4-mediated m6A in this sex-differentiated biological phenotype. Further exploration demonstrated that this sex-specific pain hypersensitivity is closely associated with sex-dependent expression of uncoupling protein 2 (UCP2) in synapses. Specifically, elevated UCP2 expr

SUBMITTER: Wu Y 

PROVIDER: S-EPMC12799839 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature