Nonsense-mediated RNA decay (NMD) is an evolutionarily conserved RNA quality control process that serves both as a mechanism to eliminate aberrant transcripts carrying premature stop codons, and to regulate expression of some normal transcripts. For a quality control process, NMD exhibits surprising variability in its efficiency across transcripts, cells, tissues, and individuals in both physiological and pathological contexts. Whether an aberrant RNA is spared or degraded, and by what mechanism, could determine the phenotypic outcome of a disease-causing mutation. Hence, understanding the variability in NMD is not only important for clinical interpretation of genetic variants but also may provide clues to identify novel therapeutic approaches to counter genetic disorders caused by nonsense mutations. Here, we discuss the current knowledge of NMD variability and the mechanisms that allow certain transcripts to escape NMD despite the presence of NMD-inducing features. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA in Disease and Development > RNA in Disease RNA Turnover and Surveillance > Regulation of RNA Stability.

中文翻译：

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如何摆脱无意义：逃避无意义介导的 RNA 衰变的机制和后果。

无义介导的 RNA 衰减 (NMD) 是一种进化上保守的 RNA 质量控制过程，它既可以作为消除携带过早终止密码子的异常转录本的机制，又可以调节某些正常转录本的表达。对于质量控制过程，NMD 在生理和病理环境下的转录本、细胞、组织和个体中表现出令人惊讶的效率差异。异常RNA是否被幸免或被降解，以及通过什么机制，可以决定致病突变的表型结果。因此，了解 NMD 的变异性不仅对于遗传变异的临床解释很重要，而且还可能为识别新的治疗方法来对抗无义突变引起的遗传性疾病提供线索。在这里，我们讨论目前对 NMD 变异性的了解，以及尽管存在 NMD 诱导特征，但仍允许某些转录本逃脱 NMD 的机制。本文分类如下：RNA 周转和监视 > 周转/监视机制 RNA 在疾病和发育中的作用 > 疾病中的 RNA RNA 周转和监视 > RNA 稳定性的调节。