Loss of m⁶A on FAM134B promotes adipogenesis in porcine adipocytes through m⁶A‐YTHDF2‐dependent way

N⁶ -methyladenosine (m⁶ A) mRNA modification plays an important role in adipogenesis, but its role on single gene remains unexplored. Family with Sequence Similarity 134, Member B (FAM134B) is a cis-Golgi transmembrane protein that known to be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Recent work has shown that FAM134B plays a pivotal role in lipid homeostasis and was identified as its significant m⁶ A level difference between Chinese local Jinhua pigs and Landrace through RNA-sequence. Here, we construct the non-m⁶ A FAM134B coding sequence (CDS) plasmid (FAM134B-MUT) and found one important m⁶ A site on its CDS. Expression of FAM134B-MUT was more effective in promoting porcine preadipocytes adipogenic differentiation and lipid deposition than wild-type FAM134B (FAM134B-WT) both in early and ultimate differentiation stage. FAM134B-MUT functions better in promoting fat deposition by upregulating peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBPα) level. The m⁶ A reader protein YTH m⁶ A RNA binding protein 2 (YTHDF2) interacts with FAM134B mRNA and down regulated its protein level. These results demonstrate that FAM134B was the target of YTHDF2, which may recognize and binds the m⁶ A site of FAM134B to reduce its mRNA lifetime and reduce its protein abundance.