MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m⁶A-YTHDF1-dependent mechanism

Intramuscular fat is considered a potential factor that is associated with meat quality in animal production and insulin resistance in humans. N⁶-methyladenosine (m⁶A) modification of mRNA plays an important role in regulating adipogenesis. However, the effects of m⁶A on the adipogenesis of intramuscular preadipocytes and associated mechanisms remain unknown. Here, we performed m⁶A sequencing to compare m⁶A methylome of the longissimus dorsi muscles (LDMs) between Landrace pigs (lean-type breed) and Jinhua pigs (obese-type breed with higher levels of intramuscular fat). Transcriptome-wide m⁶A profiling of porcine LDMs was highly conserved with humans and mice. Furthermore, we identified a unique methylated gene in Jinhua pigs named mitochondrial carrier homology 2 ( MTCH2). The m⁶A levels of MTCH2 mRNA were reduced by introducing a synonymous mutation, and adipogenesis test results showed that the MTCH2 mutant was inferior with regard to adipogenesis compared with the MTCH2 wild-type. We then found that MTCH2 protein expression was positively associated with m⁶A levels, and an YTH domain family protein 1-RNA immunoprecipitation-quantitative PCR assay indicated that MTCH2 mRNA was a target of the YTH domain family protein 1. This study provides comprehensive m⁶A profiles of LDM transcriptomes in pigs and suggests an essential role for m⁶A modification of MTCH2 in intramuscular fat regulation.-Jiang, Q., Sun, B., Liu, Q., Cai, M., Wu, R., Wang, F., Yao, Y., Wang, Y., Wang, X. MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m⁶A-YTHDF1-dependent mechanism.