N6-甲基腺苷(m⁶A)修饰是哺乳动物中最丰富、最普遍的mRNA表观遗传修饰,并在调节细胞过程和基因表达中起关键作用。目前发现m⁶A修饰可以通过调控脂肪分化的特异基因、脂肪生成关键酶等因子的表达,进而调控脂肪生成。作者就m⁶A相关酶和蛋白在脂肪生成中的作用机制以及在脂肪生成的不同阶段是如何发挥作用的作一综述,旨在为更好地理解脂肪生成以及为肥胖症的治疗提供新靶点。

[1] SHI H,WEI J,HE C.Where,when,and how:context-dependent functions of RNA methylation writers,readers,and erasers[J].Mol Cell,2019,74(4):640-650.
[2] ROSEN E D,MACDOUGALD O A.Adipocyte differentiation from the inside out[J].Nat Rev Mol Cell Biol,2006,7(12):885-896.
[3] PENG X,ZHANG Q,LIAO C,et al.Epigenomic control of thermogenic adipocyte differentiation and function[J].Int J Mol Sci,2018,19(6):1793.
[4] WANG X,SUN B,JIANG Q,et al.mRNA m⁶A plays opposite role inregulating UCP2 and PNPLA2 protein expression in adipocytes[J].Int J Obes(Lond),2018,42(11):1912-1924.
[5] LIU J,YUE Y,HAN D,et al.A METTL3-METTL14 complex mediatesmammalian nuclear RNA N6-adenosine methylation[J].Nat Chem Biol,2014,10(2):93-95.
[6] JIA G,FU Y,ZHAO X,et al.N6-methyladenosine in nuclear RNAis a major substrate of the obesity-associated FTO[J].Nat Chem Biol,2011,7(12):885-887.
[7] HUANG Y,YAN J,LI Q,et al.Meclofenamic acid selectively inhibits FTO demethylation of m⁶A over ALKBH5[J].Nucleic Acids Res,2015,43(1):373-384.
[8] MA C,LIAO S,ZHU Z.Crystal structure of human YTHDC2 YTH domain[J].Biochem Biophys Res Commun,2019,518(4):678-684.
[9] RIES R J,ZACCARA S,KLEIN P,et al.M⁶A enhances the phase separation potential of mRNA[J].Nature,2019,571(7765):424-428.
[10] LIU J,GAO M,HE J,et al.The RNA m⁶A reader YTHDC1 silences retrotransposons and guards ES cell identity[J].Nature,2021,591(7849):322-326.
[11] ROUNDTREE I A,EVANS M E,PAN T,et al.Dynamic RNA modifications in gene expression regulation[J].Cell,2017,169(7):1187-1200.
[12] ZHAO B S,ROUNDTREE I A,HE C.Post-transcriptional gene regulation by mRNA modifications[J].Nat Rev Mol Cell Biol,2017,18(1):31-42.
[13] WU Y,XIE L,WANG M,et al.METTL3-mediated m⁶A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis[J].Nat Commun,2018,9(1):4772.
[14] YAO Y,BI Z,WU R,et al.METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m⁶A-YTHDF2-dependent manner[J].FASEB J,2019,33(6):7529-7544.
[15] KOBAYASHI M,OHSUGI M,SASAKO T,et al.The RNA methyltransferase complex of WTAP,METTL3,and METTL14 regulates mitotic clonal expansion in adipogenesis[J].Mol Cell Biol,2018,38(16):e00116-e00118.
[16] LIU Q,ZHAO Y,WU R,et al.ZFP217 regulates adipogenesisbycontrolling mitotic clonal expansion in a METTL3-m⁶A dependent manner[J].RNA Biol,2019,16(12):1785-1793.
[17] AGUILAR V,FAJAS L.Cycling through metabolism[J].EMBO Mol Med,2010,2(9):338-348.
[18] WU R,LIU Y,YAO Y,et al.FTO regulates adipogenesis by controlling cell cycle progression via m⁶A-YTHDF2 dependent mechanism[J].Biochim Biophys Acta Mol Cell Biol Lipids,2018,1863(10):1323-1330.
[19] WU R,GUO G,BI Z,et al.m⁶A methylation modulates adipogenesis through JAK2-STAT3-C/EBPβsignaling[J].BiochimBiophys Acta Gene Regul Mech,2019,1862(8):796-806.
[20] WU R,CHEN Y,LIU Y,et al.m⁶A methylation promotes white-to-beige fat transition by facilitating Hif1a translation[J].EMBO Rep,2021,22(11):e52348.
[21] WANG L,SONG C,WANG N,et al.NADP modulates RNA m⁶A methylation and adipogenesis via enhancing FTO activity[J].Nat Chem Biol,2020,16(12):1394-1402.
[22] WANG X,WU R,LIU Y,et al.m⁶A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7[J].Autophagy,2020,16(7):1221-1235.
[23] SHEN Z,LIU P,SUN Q,et al.FTO inhibits UPR^mt-induced apoptosis by activating JAK2/STAT3 pathway and reducing m⁶A level in adipocytes[J].Apoptosis,2021,26(7-8):474-487.
[24] SONG T,YANG Y,WEI H,et al.Zfp217 mediates m6A mRNA methylation to orchestrate transcriptional and post-transcriptional regulation to promote adipogenicdifferentiation[J].Nucleic Acids Res,2019,47(12):6130-6144.
[25] CHEN Y,WU R,CHEN W,et al.Curcumin prevents obesity by targeting TRAF4-induced ubiquitylation in m⁶A-dependent manner[J].EMBO Rep,2021,22(5):e52146.
[26] CAI M,LIU Q,JIANG Q,et al.Loss of m⁶ A on FAM134B promotes adipogenesis in porcine adipocytes through m⁶ A-YTHDF2-dependent way[J].IUBMB Life,2019,71(5):580-586.
[27] JIANG Q,SUN B,LIU Q,et al.MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m⁶A-YTHDF1-dependent mechanism[J].FASEB J,2019,33(2):2971-2981.