遗传 ›› 2012, Vol. 34 ›› Issue (8): 935-942.doi: 10.3724/SP.J.1005.2012.00935

• 综述 •    下一篇

无义介导的mRNA降解机制及其在单基因遗传病中的作用

郭文婷, 徐汪洋, 顾鸣敏   

  1. 上海交通大学医学院医学遗传学教研室, 上海 200025
  • 收稿日期:2012-02-15 修回日期:2012-04-17 出版日期:2012-08-20 发布日期:2012-08-25
  • 通讯作者: 顾鸣敏 E-mail:gumm@sjtu.edu.cn
  • 基金资助:

    国家自然科学基金项目(编号:30470951, 31071107)资助

Nonsense-mediated mRNA decay and human monogenic disease

GUO Wen-Ting, XU Wang-Yang, GU Ming-Min   

  1. Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Received:2012-02-15 Revised:2012-04-17 Online:2012-08-20 Published:2012-08-25

摘要: 无义介导的mRNA降解(Nonsense-mediated mRNA decay, NMD)是一种广泛存在于真核生物细胞中的mRNA质量监控机制。该机制通过识别和降解含有提前终止密码子(Premature translational-termination codon, PTC)的转录产物防止有潜在毒性的截短蛋白的产生。据估计, 约1/3的遗传性疾病是由提前终止密码子引起的, 而NMD作用通常会改变某些遗传病的临床症状或遗传方式。文章主要综述了人体细胞中NMD对底物的识别及其作用机制, 并以几种单基因遗传病为例探讨其对这些疾病表型的影响, 表明NMD作用机制的进一步揭示将有助于单基因遗传病发病机制的阐明及治疗方法的改进。

关键词: 无义介导的mRNA降解(NMD), 提前终止密码子(PTC), 截短蛋白, 人类单基因遗传病

Abstract: Nonsense-mediated mRNA decay (NMD) is a widespread quality control mechanism in eukaryotic cells. It can recognize and degrade aberrant transcripts harbouring a premature translational termination codon (PTC), and thereby prevent the production of C-terminally truncated proteins which might be deleterious. Approximately, 30% of human genetic diseases are caused by transcripts containing PTCs. These transcripts are potential targets of NMD. As for monogenic diseases, NMD has effects on the phenotype or mode of inheritance. Here, we explain the mechanism of this surveillance pathway, and take several neuromuscular disorders as examples to discuss its influence for human monogenic diseases. The deeper understanding for NMD will shed light on the nosogenesis and therapies of monogenic diseases.

Key words: nonsense-mediated mRNA decay (NMD), premature translation-termination codon (PTC), truncated proteins, human monogenic diseases