N-6甲基腺嘌呤RNA甲基化调控骨髓间充质干细胞的成骨及成脂分化

N-6 methyladenosine RNA methylation regulates osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells

背景:N-6甲基腺嘌呤是真核生物mRNA中最常见、含量最丰富的一种RNA修饰,其通过甲基化修饰基因片段上的碱基位点,从而影响RNA的翻译、剪切、表达与降解等生物学功能。骨髓间充质干细胞作为一种非造血干细胞,具有多向分化潜能,在各类骨相关疾病中具有良好的应用前景。目的:归纳总结各类N-6甲基腺嘌呤修饰酶在骨髓间充质干细胞成骨及成脂分化中的功能及相关作用机制,简要概括N-6甲基腺嘌呤的研究方法及研究展望,为基因靶向治疗骨代谢相关疾病提供重要参考。方法:通过检索PubMed、Web of Science、中国知网等数据库,英文关键词为"m6A,bone marrow mesenchyml stem cell",中文关键词为"m6A,骨髓间充质干细胞",最终纳入46篇文献进行综述。结果与结论:(1)N-6甲基腺嘌呤修饰的发生主要由甲基转移酶复合物、去甲基化酶和识别N-6甲基腺嘌呤特定家族蛋白酶共同调节;(2)N-6甲基腺嘌呤各类修饰酶能从基因水平影响骨髓间充质干细胞的生物学特性;(3)N-6甲基腺嘌呤与骨髓间充质干细胞成骨及成脂相关信号传导通路存在调控机制关系;(4)N-6甲基腺嘌呤在骨髓间充质干细胞相关再生医学领域中具有较大的发展潜能。

BACKGROUND:N-6 methyladenosine is one of the most common and abundant RNA modifications in eukaryotic mRNA.It modifies the base sites on gene fragments through methylation,affecting the biological functions of RNA such as translation,splicing,expression and degradation.Bone marrow mesenchymal stem cells,a kind of non-hematopoietic stem cells,have potential of multidirectional differentiation and show great application prospects in various bonerelated diseases.OBJECTIVE:To summarize the functions and related mechanisms of various m6A modifying enzymes in osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells,and to briefly introduce the research methods and prospects of N-6 methyladenosine,so as to provide important reference for gene targeted therapy of bone metabolism-related diseases.METHODS:By searching several domestic and foreign literature databases,such as PubMed,Web of Science and CNKI.The key words were"m6A,bone marrow mesenchyml stem cell"both in English and Chinese.Finally,46 articles were included for review.RESULTS AND CONCLUSION:The occurrence of N-6 methyladenosine modification is mainly regulated by methyltransferase complex,demethylase and N-6 methyladenosine-specific protease.N-6 methyladenosine modifiers can affect the biological characteristics and functions of bone marrow mesenchymal stem cells at the gene level.There is a regulatory relationship between N-6 methyladenosine and signal transduction pathways related to osteogenic and adipogenic of bone marrow mesenchymal stem cells.N-6 methyladenosine has great potential in the field of bone marrow mesenchymal stem cells related regenerative medicine.