METTL14 Promotes Chicken Preadipocyte Differentiation by Modulating mRNA Stability via a Dual-Reader m6A Mechanism.

Preadipocyte differentiation is an essential process in adipogenesis. METTL14, an essential constituent of the N6-methyladenosine (m6A) methyltransferase complex, plays an important role in mammalian preadipocyte differentiation. However, its role in avian adipogenesis remains unclear. More importantly, the m6A mechanism by which METTL14 regulates preadipocyte differentiation has not been elucidated. Here, we found that the level of METTL14 expression was substantially elevated within the adipose tissue of the abdominal region of fat chickens relative to lean chickens. Knockdown of METTL14 inhibited preadipocyte differentiation, whereas overexpression of METTL14 promoted this process. Through the integration of MeRIP-seq and RNA-seq, we confirmed that chBMI1, chTMED3, and chMFAP2 were functionally essential targets of METTL14-dependent m6A modification in adipogenesis. METTL14-mediated chBMI1 mRNA stabilization and the degradation of chTMED3 and chMFAP2 mRNAs depend on IGF2BP1/2 and YTHDF2, respectively. Overall, our findings establish that METTL14 promotes chicken preadipocyte differentiation by modulating the stability of target mRNAs through a dual-reader m6A mechanism.