GPCPD1 is regulated by METTL3/IGF2BP3 dependent mA modification to affect pig muscle fiber type conversion.

The N6-methyladenosine (mA) modification is the most prevalent and abundant RNA modification in eukaryotes. In our previous study, we identified that the glycerophosphocholine phosphodiesterase 1 (GPCPD1) gene was differentially expressed and diverse mA modificated in the pig soleus and extensor digitorum longus muscles. In this study, we further investigated the function of GPCPD1 gene in pig muscle development. We found that GPCPD1 inhibited myogenic differentiation and promoted the conversion of fast-twitch to slow-twitch fibers in both porcine muscle satellite cells (PSCs) and in mouse model. We also found that the expression of GPCPD1 was affected by mA methyltransferase METTL3. The methylated GPCPD1 gene was recognized by the mA reader protein IGF2BP3, which further modulated the stability of GPCPD1 mRNA. This study provided novel evidence into mA regulation in pig muscle development and illustrated the new post-transcriptional regulation way in GPCPD1 expression.