FTO regulates adipogenesis by controlling cell cycle progression via m6A-YTHDF2 dependent mechanism

METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m 6 A‐YTHDF2–dependent manner

“…Wang et al (44) reported that m 6 A modification affects the translation of patatin like phospholipase domain containing 2 (PNPLA2) and uncoupling protein 2 (UCP2) to regulate adipogenesis. Wu et al (53,54) reported that fat mass and obesity-associated gene (FTO) and YTHDF2 cooperatively mediate cyclin A2 (CCNA2) and cyclin dependent kinase 2 (CDK2) expression through m 6 A methylation, further influencing cell cycle progression and adipogenesis. METTL3, as a methyltransferase, catalyzes the formation of m 6 A and plays important roles in various biologic processes (23,55).…”

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

“…Suppressing adipogenesis by promoting cell cycle transition in mitotic clonal expansion [89] YTHDF2 Inhibiting autophagy and adipogenesis by decreasing protein expression of ATG5 and ATG7 and shortening the lifespan of their m 6 A-modified mRNAs [87] Suppressing adipogenesis by increasing m 6 A methylation of CCNA2 and CDK2 and reversing the methylation effect of FTO on CCNA2 and CDK2 [90,91] Inhibiting adipogenesis via the downregulation of CCND1 [92] NAFLD FTO Down-regulating mitochondrial content and up-regulating TG deposition [101] Promoting hepatic fat accumulation by increasing the expression of lipogenic genes, including FASN, SCD and MOGAT1, and intracellular TG level in HepG2 cells [101] Increasing oxidative stress and lipid deposition [99] YTHDF2 Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression [105] METTL3 Increasing lipid accumulation by decreasing both PPARα mRNA lifetime and expression [105] Hypertension m 6 A-SNPs EncodIing β1-adrenoreceptor, a hypertension-susceptibility candidate gene [108,109] Altering BP-related gene expression, mRNA stability and homeostasis [110] Cardiovascular diseases FTO Decreasing fibrosis and enhancing angiogenesis in mouse models of myocardial infarction [111] METTL3 Driving cardiomyocyte hypertrophy by catalyzing methylation of m 6 A on certain subsets of mRNAs [112] Decreasing eccentric cardiomyocyte remodeling and dysfunction [112] Inhibiting cellular autophagic flux and promoting apoptosis in hypoxia/reoxygenation-treated cardiomyocytes [113] Osteoporosis METTL3 Inhibiting adipogenesis and adipogenic differentiation via JAK1/STAT5/C/EBPβ pathway in bone marrow stem cells [119] Inhibiting osteoporosis pathological phenotypes, consisting of decreased bone mass and increased marrow adiposity via PTH/PTH1R signaling axis [118] FTO Promoting the differentiation of adipocyte and osteoblast by upregulating GDF11-FTO-PPARγ signalling way [116] Enhancing the stability of mRNA of proteins which function to protect osteoblasts from genotoxic damage through Hspa1a-NF-κB signaling way [120] Immune-related MDs ALKBH5 Expressing highly in organs enriched in immune cells with frequent immune reactions [10,123] METTL3 Stimulating T cell activation and the development of T lymphocytes in the thymus by regulating the translation of CD40, CD80 and TLR4 signaling adaptor TIRAP transcripts in den...…”

“…In the contrast, WTAP, METTL3, METTL14 are negatively related with adipogenesis by promoting cell cycle transition in mitotic clonal expansion [88,89]. Moreover, m 6 A-YTHDF2-FTO signaling way might be crucial for the development of obesity, m 6 A-binding protein YTHDF2 can methylate mRNAs of cyclin A2 (CCNA2) and cyclin dependent kinase 2 (CDK2), and then reduce their protein expression to prolong cell cycle progression and suppress adipogenesis [90]. The methylation effect of FTO on CCNA2 and CDK2 can be reversed by epigallocatechin gallate induced YTHDF2 expression [91].…”

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

“…It binds to the peroxisome proliferator-activated receptor α to mediate its mRNA stability to regulate lipid metabolism [105]. It recognized and decayed methylated mRNAs of Cyclin-A2 and kinase CDK2, thereby prolonging cell cycle progression and suppressing adipogenesis [106]. YTHDF2 plays an important role in regulating hematopoietic stem cells ex vivo expansion by regulating the stability of multiple mRNAs critical for HSC self-renewal of these cells [107].…”