无义介导的mRNA降解在胚胎发育中的作用及机制的研究进展
宣丽娜, 沈细亚, 王鹏, 杜雷雷, 张帆, 徐星星, 黄智慧^*
温州医科大学基础医学院神经科学研究所，温州 325035
摘要
无义介导的mRNA降解(nonsense-mediated mRNA decay, NMD)最初被认为是一种广泛存在的mRNA质量监控机制，可迅速降解含有提前终止密码子的异常mRNA，避免有害的、截短的蛋白产物积累而对细胞造成损害。最近研究显示，NMD也可以调控执行重要细胞生理功能的正常基因转录物的降解过程，因此被认为是真核生物中高度保守的转录后调节机制。NMD直接或间接调控从酵母到人的3%~20%的转录组，对于细胞稳态、应激反应、增殖、分化等多种生理活动都是必不可少的。研究表明，NMD可以调节与发育相关的转录物的水平，NMD因子敲除大多具有胚胎致死效应。NMD在胚胎干细胞的自我更新、分化与胚胎发育的过程中发挥重要作用。本文将对NMD在胚胎发育中的作用及机制的最新研究进展进行综述，以期为胚胎发育的研究和胚胎发育相关疾病的治疗提供新的思路。


关键词： 无义介导的mRNA降解; 提前终止密码子; 胚胎干细胞; 自我更新; 分化; 胚胎发育
分类号：Q291; Q944.46

Advances in the roles and mechanisms of nonsense-mediated mRNA decay in embryonic development
XUAN Li-Na, SHEN Xi-Ya, WANG Peng, DU Lei-Lei, ZHANG Fan, XU Xing-Xing, HUANG Zhi-Hui^*
Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China
Abstract
Nonsense-mediated mRNA decay (NMD) is originally identified as a widespread mRNA surveillance machinery in degrading ‘aberrant’ mRNA species with premature termination codons (PTCs) rapidly, which protects the cells from the accumulation of truncated proteins. Recent studies show that NMD can also regulate the degradation of normal gene transcripts, which execute important cellular and physiological functions. Therefore, NMD is considered as a highly conserved post-transcriptional regulatory mechanism in eukaryotes. NMD modulates 3% to 20% of the transcriptome from yeast to human directly or indirectly, which is essential for various physiological processes, such as cell homeostasis, stress response, proliferation, and differentiation. NMD can regulate the level of transcripts that involves in development, and single knockout of most NMD factors has an embryonic lethal effect. NMD plays an important role in the self-renewal, differentiation of embryonic stem cells and is critical during embryonic development. In this review, we summarized the latest advances in the roles and mechanisms of NMD in embryonic development, in order to provide new ideas for the research on embryonic development and the treatment of embryonic development related diseases.


Key words: nonsense-mediated mRNA decay; premature termination codons; embryonic stem cells; Self-renewal; differentiation; embryonic development

收稿日期：2018-05-30　　录用日期：2018-10-24
通讯作者：黄智慧　　E-mail: hzhzju021@163.com
DOI: 10.13294/j.aps.2019.0019
引用本文：
宣丽娜, 沈细亚, 王鹏, 杜雷雷, 张帆, 徐星星, 黄智慧. 无义介导的mRNA降解在胚胎发育中的作用及机制的研究进展[J]. 生理学报 2019; 71 (2): 327-335.
XUAN Li-Na, SHEN Xi-Ya, WANG Peng, DU Lei-Lei, ZHANG Fan, XU Xing-Xing, HUANG Zhi-Hui. Advances in the roles and mechanisms of nonsense-mediated mRNA decay in embryonic development. Acta Physiol Sin 2019; 71 (2): 327-335 (in Chinese with English abstract).



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