The role of goat FTO/IGF2BP1-mediated BCL11A m6A modification in intramuscular adipocyte differentiation
TL;DR
Findings reveal that FTO and IGF2BP1 co-regulate the differentiation of intramuscular adipocytes through post-transcriptional modification of BCL11A, providing novel insights into m6A-mediated lipid deposition in goat muscle.
Abstract
Intramuscular fat (IMF) plays a critical role in determining the flavor of goat meat. Studies have shown that N6-methyladenosine (m6A) modification of mRNA exerts a key influence on adipocyte differentiation and lipid metabolism. However, whether m6A−modified mRNA regulates the differentiation of intramuscular adipocytes in goats remains unclear. This study constructed the m6A methylation landscape during the differentiation of goat intramuscular adipocytes using MeRIP-seq and RNA-seq, and identified BCL11A as a key regulator exhibiting synchronized changes in both m6A modification and expression. Functional assays demonstrated that BCL11A promotes lipid accumulation and upregulates adipogenic markers ( C/EBPα , PPARγ , SREBP1 , FASN ). Mechanistically, the demethylase FTO directly targets the m6A site on BCL11A , while the reader protein IGF2BP1 recognizes this modification and reduces BCL11A mRNA stability. FTO promotes adipogenesis, whereas knockdown of IGF2BP1 shortens the half-life of BCL11A and inhibits differentiation. These findings reveal that FTO and IGF2BP1 co-regulate the differentiation of intramuscular adipocytes through post-transcriptional modification of BCL11A , providing novel insights into m6A-mediated lipid deposition in goat muscle.