Loss of m6A on FAM134B promotes adipogenesis in porcine adipocytes through m6A-YTHDF2-dependent way
Loss of m6A on FAM134B promotes adipogenesis in porcine adipocytes through m6A-YTHDF2-dependent way
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DOI：
10.1002/iub.1974
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发表时间：
2019-05-01
期刊：
影响因子：
4.6
通讯作者：
Wang, Yizhen
中科院分区：
文献类型：
--
作者：
Cai, Min;Liu, Qing;Wang, Yizhen
N-6-甲基腺苷 (m(6)A) mRNA 修饰在脂肪形成中发挥重要作用，但其对单个基因的作用仍未被探索。序列相似性家族 134，成员 B (FAM134B) 是一种顺式高尔基体跨膜蛋白，已知对于伤害性神经节和自主神经节神经元的长期存活是必需的。最近的工作表明，FAM134B 在脂质稳态中发挥着关键作用，并通过 RNA 序列鉴定出其在中国本地金华猪和长白猪之间的显着 m(6)A 水平差异。在此，我们构建了非m(6)A FAM134B编码序列(CDS)质粒(FAM134B-MUT)，并在其CDS上发现了一个重要的m(6)A位点。在早期和最终分化阶段，FAM134B-MUT的表达比野生型FAM134B（FAM134B-WT）更能有效地促进猪前脂肪细胞的成脂分化和脂质沉积。 FAM134B-MUT 通过上调过氧化物酶体增殖物激活受体 γ (PPAR γ) 和 CCAAT/增强子结合蛋白 (C/EBP α) 水平，更好地促进脂肪沉积。 m(6)A 阅读器蛋白 YTH m(6)A RNA 结合蛋白 2 (YTHDF2) 与 FAM134B mRNA 相互作用并下调其蛋白水平。这些结果表明FAM134B是YTHDF2的靶标，YTHDF2可能识别并结合FAM134B的m(6)A位点，以减少其mRNA寿命并降低其蛋白质丰度。 (c) 2018 IUBMB 生活，71(5):580-586，2019
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