Eukaryotes have evolved a variety of mRNA surveillance mechanisms to detect and degrade aberrant mRNAs with potential deleterious outcomes. Among them, nonsense-mediated mRNA decay (NMD) functions not only as a quality control mechanism targeting aberrant mRNAs containing a premature termination codon but also as a posttranscriptional gene regulation mechanism targeting numerous physiological mRNAs. Despite its well-characterized molecular basis, the regulatory scope and biological functions of NMD at an organismal level are incompletely understood. In humans, mutations in genes encoding core NMD factors cause specific developmental and neurological syndromes, suggesting a critical role of NMD in the central nervous system. Here, we review the accumulating biochemical and genetic evidence on the developmental regulation and physiological functions of NMD as well as an emerging role of NMD dysregulation in neurodegenerative diseases.

中文翻译：

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神经发育和疾病中无义介导的 mRNA 衰变的调节

真核生物已经进化出多种 mRNA 监测机制来检测和降解具有潜在有害结果的异常 mRNA。其中，无义介导的 mRNA 衰变 (NMD) 不仅作为一种针对含有提前终止密码子的异常 mRNA 的质量控制机制，而且作为一种针对众多生理 mRNA 的转录后基因调控机制。尽管其具有良好表征的分子基础，但 NMD 在有机体水平上的调节范围和生物学功能尚不完全清楚。在人类中，编码核心 NMD 因子的基因突变会导致特定的发育和神经系统综合征，这表明 NMD 在中枢神经系统中的关键作用。这里，