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

N-6-methyladenosine (m(6)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 m(6)A level difference between Chinese local Jinhua pigs and Landrace through RNA-sequence. Here, we construct the non-m(6)A FAM134B coding sequence (CDS) plasmid (FAM134B-MUT) and found one important m(6)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 gamma (PPAR gamma) and CCAAT/enhancer-binding protein (C/EBP alpha) level. The m(6)A reader protein YTH m(6)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 m(6)A site of FAM134B to reduce its mRNA lifetime and reduce its protein abundance. (c) 2018 IUBMB Life, 71(5):580-586, 2019