m^(6)A甲基化在骨骼肌发育中的生物学作用及调控机制研究进展  

Research Progress on the Biological Role and Regulatory Mechanism of m^(6)A Methylation in Skeletal Muscle Development

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作  者:何思琦 陈倩 张贺春 陈红艳[4] 马月辉[1] 周胜花 赵倩君[1] HE Siqi;CHEN Qian;ZHANG Hechun;CHEN Hongyan;MA Yuehui;ZHOU Shenghua;ZHAO Qianjun(Institute of Animal Science of CAAS,Beijing 100193,China;College of Animal Science,Shanxi Agricultural University,Taigu 030801,China;Chaoyang Chaomu Breeding Farm Co.,Ltd.,Chaoyang 122629,China;Yunnan Agricultural Vocational and Technical College,Kunming 650000,China)

机构地区:[1]中国农业科学院北京畜牧兽医研究所,北京100193 [2]山西农业大学动物科学学院,太谷030801 [3]朝阳市朝牧种畜场有限公司,朝阳122629 [4]云南农业职业技术学院,昆明650000

出  处:《中国畜牧兽医》2025年第4期1511-1521,共11页China Animal Husbandry & Veterinary Medicine

基  金:国家自然科学基金面上项目(32172701);国家绒毛用羊产业技术体系项目(CARS-39)。

摘  要:N6-甲基腺苷修饰(N6-methyladenosine, m^(6)A),即RNA腺嘌呤A碱基的第6位氮原子发生甲基化,是真核生物细胞中最普遍和最丰富的RNA修饰。动态可逆的m^(6)A修饰由甲基转移酶样3(METTL3)及其辅助因子组成的甲基转移酶复合物催化,脂肪质量和肥胖相关基因(FTO)、ALKB同源基因5(ALKBH5)等去甲基化酶消除RNA甲基化修饰信号,并通过m^(6)A结合蛋白识别RNA m^(6)A修饰位点。m^(6)A修饰能够调控RNA的剪接、出核、翻译和稳定性等分子调节作用,已成为表观遗传学领域的研究热点。骨骼肌是动物机体重要的组成部分,其发育涉及成肌细胞增殖、迁移、分化和融合形成肌管细胞,进而形成肌肉纤维等多个过程,受多种转录因子及表观遗传调控。其中,m^(6)A甲基化修饰参与调控肌肉干细胞的维持、成肌细胞增殖及分化。越来越多研究表明,由m^(6)A甲基化修饰介导的转录及转录后调控在骨骼肌生长发育中起着至关重要的调控作用。作者介绍了m^(6)A甲基化修饰酶的种类及作用,重点综述了m^(6)A甲基化修饰在骨骼肌生长发育及相关疾病中的调控机制,为解析肌肉发育表观调控机制及发现潜在的骨骼肌疾病治疗靶点等研究提供新思路。N6-methyladenosine(m^(6)A),the RNA methylation of the 6th nitrogen atom of the adenine A base group,is the most common and abundant RNA modification in eukaryotic cells.The dynamic and reversible m^(6)A modification is catalyzed by a methyltransferase complex composed of methyltransferase-like 3(METTL3)and its cofactors.The RNA methylation modification signal is eliminated by demethylases such as fat mass and obesity-associated protein(FTO)and ALKB homolog 5(ALKBH5),and the m^(6)A modification site is recognized by m^(6)A binding proteins.m^(6)A modification has become a research hotspot in the field of epigenetics,as it can regulate molecular regulatory effects such as RNA splicing,enucleation,translation and stability.Skeletal muscle is an important component of the animal body,and its development involves multiple processes such as proliferation,migration,differentiation and fusion of myoblasts to form myotubes,which in turn form muscle fibers,it is regulated by various transcription factors and epigenetics.Among them,m^(6)A methylation modification plays a role in regulating the maintenance,proliferation,and differentiation of muscle stem cells.Recent studies have shown that transcription and post-transcriptional regulation mediated by m^(6)A methylation play a crucial role in the growth and development of skeletal muscle.The authors introduce the types and functions of m^(6)A methylation modification enzymes,and with a focus on summarizing the regulatory effects and mechanisms of m^(6)A methylation modification in skeletal muscle growth,development and related diseases,so as to provide new ideas for analyzing the epigenetic regulation mechanism of muscle development and discovering potential therapeutic targets for skeletal muscle diseases.

关 键 词:m^(6)A甲基化 m^(6)A甲基化修饰酶 骨骼肌 调控机制 

分 类 号:S852.2[农业科学—基础兽医学]

 

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