遗传 ›› 2014, Vol. 36 ›› Issue (3): 248-255.doi: 10.3724/SP.J.1005.2014.0248

• 综述 • 上一篇    下一篇

表观遗传调控pre-mRNA的选择性剪接

赵金璇, 王芳, 徐峥嵘, 范怡梅   

  1. 南京大学医学院医学遗传学研究室, 南京210093
  • 收稿日期:2013-09-30 修回日期:2013-11-12 出版日期:2014-03-20 发布日期:2014-02-25
  • 通讯作者: 范怡梅, 博士, 副教授, 研究方向:肿瘤遗传学。E-mail: ymfan@nju.edu.cn E-mail:ymfan@nju.edu.cn
  • 作者简介:赵金璇, 硕士研究生, 专业方向:临床医学。Tel: 15996235562; E-mail: njuzhaojinxuan@163.com
  • 基金资助:

    国家自然科学基金面上项目(编号:30972535), 江苏省自然科学基金面上项目(编号:BK2012724)和南京大学大学生创新创业训练计划项目(编号:G1310284100)资助

The epigenetic effect on pre-mRNA alternative splicing

Department of Medical Genetics, Medical School, Nanjing University, Nanjing 210093, China   

  1. Department of Medical Genetics, Medical School, Nanjing University, Nanjing 210093, China
  • Received:2013-09-30 Revised:2013-11-12 Online:2014-03-20 Published:2014-02-25
  • Contact: FAN YIMEI E-mail:ymfan@nju.edu.cn

摘要:

选择性剪接是真核生物基因表达过程中的关键环节, 是蛋白质多样性的主要来源, 在生物的分化、发育及疾病的发生中扮演重要角色。传统的选择性剪接调控机制的研究多集中于RNA序列元件及与之相关的一些剪接因子, 但近期的突破性研究指出表观遗传因素在选择性剪接的调控中发挥重要作用。DNA甲基化、染色质结构、组蛋白修饰相互影响并作用于pre-mRNA的选择性剪接, 构成一个庞大、复杂的调控网络, 表明表观遗传因素不仅决定着基因转录的起始, 还影响其转录本剪接的结果。文章综述了近年来pre-mRNA选择性剪接的表观遗传调控的研究进展, 探讨了DNA甲基化、染色质结构、组蛋白修饰在pre-mRNA选择性剪接中的可能作用, 并展望了其对人类疾病研究所带来的深远影响。

关键词: 选择性剪接, RNAⅡ型聚合酶, DNA甲基化, 组蛋白修饰, 染色质结构

Abstract:

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.

Key words: alternative splicing, RNA polymeraseⅡ, DNA methylation, histone modification, chromatin structure