Zhao Jinxuan, Wang Fang, Xu Zhengrong, Fan Yimei
Department of Medical Genetics, Medical School, Nanjing University, Nanjing 210093, China.
Yi Chuan. 2014 Mar;36(3):248-55.
Alternative splicing is a crucial step of the gene expression process in eukaryotes. It is a major cause for protein diversity and plays critical roles in differentiation, development, and disease. The studies on the mechanism of alternative splicing have traditionally focused on RNA sequence elements and their related splicing factors, but recent groundbreaking studies have shown that epigenetic factors play a key role in alternative splicing regulation. DNA methylation, chromatin structure and histone modifications interact with each other and regulate the process of alternative pre-mRNA splicing, forming a large and complex regulatory network. These findings suggest that epigenetic regulation not only determines the initiation of gene expression but also influences the outcome of pre-mRNA splicing. This review mainly focuses on the recent research progress in epigenetic regulation of pre-mRNA alternative splicing, including the functions of DNA methylation, chromatin structure and histone modifications in pre-mRNA alternative splicing, and speculates on its far-reaching effects on the study of human disease.
可变剪接是真核生物基因表达过程中的关键步骤。它是蛋白质多样性的主要原因，在分化、发育和疾病中发挥着关键作用。传统上，关于可变剪接机制的研究主要集中在RNA序列元件及其相关的剪接因子上，但最近的开创性研究表明，表观遗传因素在可变剪接调控中起关键作用。DNA甲基化、染色质结构和组蛋白修饰相互作用，调节前体mRNA可变剪接过程，形成一个庞大而复杂的调控网络。这些发现表明，表观遗传调控不仅决定基因表达的起始，还影响前体mRNA剪接的结果。本综述主要关注前体mRNA可变剪接表观遗传调控的最新研究进展，包括DNA甲基化、染色质结构和组蛋白修饰在前体mRNA可变剪接中的作用，并推测其对人类疾病研究的深远影响。
