FTO-mediated m⁶A demethylation regulates GnRH expression in the hypothalamus via the PLCβ3/Ca²⁺/CAMK signalling pathway.

ABSTRACT: N⁶-methyladenosine (m⁶A) plays a crucial role in the development and functional homeostasis of the central nervous system. The fat mass and obesity-associated (FTO) gene, which is highly expressed in the hypothalamus, is closely related to female pubertal development. In this study, we found that m⁶A methylation decreased in the hypothalamus gradually with puberty and decreased in female rats with precocious puberty. FTO expression was increased at the same time. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed that the m⁶A methylation of PLCβ₃, a key enzyme of the Ca²⁺ signalling pathway, was decreased significantly in the hypothalamus in precocious rats. Upregulating FTO increased PLCβ3 expression and activ

SUBMITTER: Zang S 

PROVIDER: S-EPMC10739951 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature