Progress in research on m6A modification of FTO mediated-RNA and development

doi:10.16352/j.issn.1001-6325.2022.10.1591

Abstract

Abstract: Human fat mass and obesity associated protein FTO is the first confirmed N⁶-methyladenosine(m6A) demethylase, which demonstrated the existence of reversible RNA modification, and also unveiled the prelude of m6A modification research. More and more researchers have tried to explore the specific mechanism of gene expression regulation at the level of m6A modification. It is found that m6A modification function requires the joint participation of methylesterase, demethylase, and binding protein to complete. FTO catalyze the demethylation of m6A modifications on mRNAs and is widely expressed in human tissues and participate in the regulation of various biological processes. This paper outlines the relationship between demethylase FTO and its mediated m6A/RNA modification and the development of body fat tissue, embryonic tissue, brain and neuro-system, hoping to gain insight into the function and mechanism of FTO.

Key words: FTO, mRNA, m6A, development

CLC Number:

R363

PAN Ming-min, WANG Qi-yang, YANG Li-ping. Progress in research on m6A modification of FTO mediated-RNA and development[J]. Basic & Clinical Medicine, 2022, 42(10): 1591-1595.

References 25

[1]	Peters T, Ausmeier K, Rüther U. Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation[J]. Mamm Genome, 1999, 10: 983-986.
[2]	Peters T, Ausmeier K, Dildrop R, et al. The mouse Fused toes (Ft) mutation is the result of a 1.6-Mb deletion including the entire Iroquois B gene cluster[J]. Mamm Genome, 2002, 13: 186-188.
[3]	Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity[J]. Science, 2007, 316: 889-894.
[4]	Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase[J]. Science, 2007, 318: 1469-1472.
[5]	Han Z, Niu T, Chang J, et al. Crystal structure of the FTO protein reveals basis for its substrate specificity[J]. Nature, 2010, 464: 1205-1209.
[6]	Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO[J]. Nat Chem Biol, 2011, 7: 885-887.
[7]	Niu Y, Lin Z, Wan A, et al. RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3[J]. Mol Cancer, 2019, 18: 46.doi: 10.1186/s12943-019-1004-4.
[8]	Zhang H, Shi X, Huang T, et al. Dynamic landscape and evolution of m6A methylation in human[J]. Nucleic Acids Res, 2020, 48: 6251-6264.
[9]	Ries RJ, Zaccara S, Klein P, et al. m(6)A enhances the phase separation potential of mRNA[J]. Nature, 2019, 571: 424-428.
[10]	Huang Y, Su R, Sheng Y, et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia[J]. Cancer Cell, 2019, 35: 677-691.
[11]	Ferenc K, Pilžys T, Garbicz D, et al. Intracellular and tissue specific expression of FTO protein in pig: changes with age, energy intake and metabolic status[J]. Sci Rep, 2020, 10: 13029.doi: 10.1038/s41598-020-69856-5.
[12]	Wang X, Wu R, Liu Y, et al. m(6)A mRNA methylation controls autophagy and adipogenesis by target-ing Atg5 and Atg7[J]. Autophagy, 2020, 16: 1221-1235.
[13]	Wang L, Song C, Wang N, et al. NADP modulates RNA m(6)A methylation and adipogenesis via enhancing FTO activity[J]. Nat Chem Biol, 2020, 16: 1394-1402.
[14]	Zhao X, Yang Y, Sun BF, et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis[J]. Cell Res, 2014, 24: 1403-1419.
[15]	Bassols J, Prats-Puig A, Vazquez-Ruiz M, et al. Placental FTO expression relates to fetal growth[J]. Int J Obes (Lond), 2010, 34: 1365-1370.
[16]	Barton SJ, Mosquera M, Cleal JK, et al. Relation of FTO gene variants to fetal growth trajectories: findings from the Southampton Women's survey[J]. Placenta, 2016, 38: 100-106.
[17]	Song T, Lu J, Deng Z, et al. Maternal obesity aggravates the abnormality of porcine placenta by increasing N6-methyladenosine[J]. Int J Obes (Lond), 2018,42:1812-1820.
[18]	Du T, Li G, Yang J, et al. RNA demethylase Alkbh5 is widely expressed in neurons and decreased during brain development[J]. Brain Res Bull, 2020, 163: 150-159.
[19]	Xue A, Huang Y, Li M, et al. Comprehensive analysis of differential m6A RNA methylomes in the hippocampus of cocaine-conditioned mice[J]. Mol Neurobiol, 2021,58:37593768.
[20]	Li L, Zang L, Zhang F, et al. Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis[J]. Hum Mol Genet, 2017, 26: 2398-2411.
[21]	Engel M, Eggert C, Kaplick PM, et al. The role of m(6)A/m-RNA methylation in stress response regulation[J]. Neuron, 2018, 99: 389-403.
[22]	Walters BJ, Mercaldo V, Gillon CJ, et al. The role of the RNA demethylase FTO (fat mass and obesity-associated) and mRNA methylation in hippocampal memory formation[J]. 2017, 42: 1502-1510.
[23]	Selberg S, Yu LY, Bondarenko O, et al. Small-molecule inhibitors of the RNA m6A demethylases FTO potently support the survival of dopamine neurons[J]. Int J Mol Sci, 2021, 22: 4537.doi: 10.3390/ijms22094537.
[24]	Chen X, Yu C, Guo M, et al. Down-regulation of m6A mRNA methylation is involved in dopaminergic neuronal death[J]. ACS Chem Neurosci, 2019, 10: 2355-2363.
[25]	Yu J, Chen M, Huang H, et al. Dynamic m6A modification regulates local translation of mRNA in axons[J]. Nucleic Acids Res, 2018, 46: 1412-1423.