Mettl14 deficiency promotes Fam32a expression via m6A modifications to facilitate the hepatocyte G1/S transition
Mettl14, a key component of the m6A methyltransferase complex, plays a crucial role in regulating mRNA stability and splicing. Reduced expression of Mettl14 is associated with hepatocellular carcinoma and liver regeneration, yet the molecular mechanisms by which it regulates the hepatocyte cell cycle remain unclear. Using RNA-Seq and MeRIP-Seq in liver-specific Mettl14 knockout mice, we found that Mettl14 deficiency stabilizes Fam32a mRNA through m6A modifications, resulting in increased Fam32a protein levels. Elevated Fam32a expression accelerates the G1/S transition by modulating Cdkn1a splicing, specifically downregulating its variant 2. These findings uncover a novel m6A-dependent mechanism that regulates hepatocyte cell cycle progression and highlight the previously unrecognized role of Fam32a in promoting the G1/S transition. Overall design: This experiment involved two sets of sequencing analyses: the first compared RNA-seq  between Mettl14-KO mice and wild-type mice, while the second analyzed RNA-seq data from AML12 cells overexpressing Fam32a versus empty vector controls.