FTO介导RNA的m6A修饰与发育的研究进展

doi:10.16352/j.issn.1001-6325.2022.10.1591

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (10): 1591-1595.doi: 10.16352/j.issn.1001-6325.2022.10.1591

FTO介导RNA的m6A修饰与发育的研究进展

潘明敏, 王启阳, 杨丽萍^*

河南中医药大学中西医结合基础学科, 河南郑州 450046

收稿日期:2021-04-25 修回日期:2021-10-15 出版日期:2022-10-05 发布日期:2022-09-23
通讯作者: * bioylp@126.com
基金资助:
国家自然科学基金(81973596)

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

PAN Ming-min, WANG Qi-yang, YANG Li-ping^*

Department of Integrated Chinese and Western Medicine, Henan University of Chinese Medicine, Zhengzhou 450046,China

Received:2021-04-25 Revised:2021-10-15 Online:2022-10-05 Published:2022-09-23
Contact: * bioylp@126.com

摘要/Abstract

摘要： 人类脂肪和肥胖相关蛋白FTO作为第一个被确证的N⁶-甲基腺苷(m6A)去甲基化酶,证明了RNA修饰存在可逆性,同时也揭开了m6A修饰的研究序幕。越来越多的学者试着从m6A修饰角度探讨基因表达调控的具体机制。m6A修饰功能需要甲基化酶、去甲基化酶、结合蛋白的共同参与完成。FTO可催化mRNA上m6A修饰的去甲基化,且在人体组织中广泛表达并参与调控多种生物学过程。本文综述去甲基化酶FTO及其介导的m6A/RNA修饰与体脂发育、胚胎发育、大脑发育、神经发育的关系,以期能够深入了解FTO的功能以及作用机制。

关键词: FTO, mRNA, m6A, 发育

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

中图分类号:

R363

潘明敏, 王启阳, 杨丽萍. FTO介导RNA的m6A修饰与发育的研究进展[J]. 基础医学与临床, 2022, 42(10): 1591-1595.

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.

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参考文献 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.

FTO介导RNA的m6A修饰与发育的研究进展

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

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