m 6A修饰对中枢神经系统功能及疾病的影响

doi:10.16288/j.yczz.20-233

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Hereditas(Beijing) ›› 2020, Vol. 42 ›› Issue (12): 1156-1167.doi: 10.16288/j.yczz.20-233

• Review • Previous Articles Next Articles

The effects of m ⁶A modification in central nervous system function and disease

Jiabin Shi^1,^2,³, Dayong Wang^1,^2,³, Qing Xia^1,^2,³, Xu Gao^1,^2,³()

^1. Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China
^2. Translational Medicine Research and Cooperation Center of Northern China, Harbin Medical University, Harbin 150081, China
^3. Heilongjiang Academy of Medical Sciences, Harbin 150081, China

Received:2020-07-21 Revised:2020-10-21 Online:2020-12-17 Published:2020-10-28
Contact: Gao Xu E-mail:gaoxu_671227@163.com
Supported by:
Supported by the National Natural Science Foundation of China Nos(81701078);Supported by the National Natural Science Foundation of China Nos(81773165);Natural Science Foundation of Heilongjiang Province of China No(QC2017090);the University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province No(UNPYSCT-2016190);China Postdoctoral Science Foundation Nos(2016M600261);China Postdoctoral Science Foundation Nos(2018T110317);the Innovative Science Research Project of Harbin Medical University No(2016JCZX37);Heilongjiang Postdoctoral Financial Assistance No(LBH-Z15163)

Abstract

Abstract:

N ⁶-methyladenosine (m ⁶A) is an important RNA modification, which is highly active in brain tissues, participates in global intracellular mRNA metabolism, and regulates gene expression and a variety of biological processes. Stable m ⁶A modification contributes to the normal embryonic brain development and memory formation and plays an important role in maintaining the functions of the central nervous system. However, changes in the level of m ⁶A modification and the expression of its related proteins cause abnormal nervous system functions, including brain tissue development retardation, axon regeneration disorders, memory changes, and stem cell renewal and differentiation disorders. Recent studies have also found that m ⁶A modification and its related proteins play key roles in the development of various nervous system diseases, such as Alzheimer's disease, Parkinson's disease, fragile X-chromosome syndrome, depression and glioblastoma. In this review, we summarize the research progresses of m ⁶A modification regulation mechanism in the central nervous system in recent years, and discusses the effects of gene expression regulation mediated by m ⁶A modification on the biological functions of the central nervous system and related diseases, thereby providing some insights on the new research targets and treatment directions for the central nervous system diseases.

Key words: N ⁶-methyladenosine (m ⁶A), central nervous system, stem cell, synapse, memory

Jiabin Shi, Dayong Wang, Qing Xia, Xu Gao. The effects of m ⁶A modification in central nervous system function and disease[J]. Hereditas(Beijing), 2020, 42(12): 1156-1167.

Figures/Tables 2

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类别	基因	功能	作用	参考文献
甲基化转移酶 (Writers)	METTL3	影响Dapk1、Fadd、Ngfr的mRNA半衰期	METTL3缺失可使m⁶A修饰异常,导致小脑发育不全、长期记忆能力减弱,影响干细胞的自我更新和分化	[10]
	METTL14	识别并影响Pten蛋白的翻译	METTL14敲除可影响轴突再生能力	[11]
	ZC3h13	ZC3h13使Zc3h13-WTAP-Virilizer-Hakai复合物留在核内,提高mESC内的mRNA m⁶A修饰水平	ZC3h13敲除将导致复合物从细胞核转移到细胞质,使m⁶A水平降低,破坏mESC自我更新并诱导进行分化	[12]
去甲基化转移酶 (Erasers)	FTO	FTO可抑制突触神经节中Syp基因mRNA的转录,降低Spy的蛋白水平	降低FTO的表达后可提高Syp蛋白水平,从而提高记忆能力	[13]
识别蛋白 (Readers)	YTHDF1	YTHDF1识别并结合发生m⁶A修饰的GRIN1、GRIN2A、GRIA1、CAMK2A、CAMK2B基因的mRNA,促进翻译过程	YTHDF1缺失引起相关蛋白的翻译异常,导致记忆力下降	[14]
识别蛋白 (Readers)	YTHDF3	YTHDF3可特异性识别胞浆中发生m⁶A修饰的Apc基因mRNA,与YTHDF1共同调控翻译过程	YTHDF1和YTHDF3缺失引起Apc蛋白翻译异常,可导致神经元发育异常,突触传递能力降低	[15]

The effects of m ⁶A modification in central nervous system function and disease

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