Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
RNA Bioscience Initiative, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Wiley Interdiscip Rev RNA. 2020 Jan;11(1):e1560. doi: 10.1002/wrna.1560. Epub 2019 Jul 29.
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.
无意义介导的 RNA 衰减（NMD）是一种进化上保守的 RNA 质量控制过程，它既是一种消除携带过早终止密码子的异常转录本的机制，也是调节一些正常转录本表达的机制。作为一种质量控制过程，NMD 在生理和病理环境下，在跨转录本、细胞、组织和个体中的效率表现出惊人的可变性。异常的 RNA 是被保留还是被降解，以及通过什么机制，可能决定致病突变的表型结果。因此，了解 NMD 的可变性不仅对遗传变异的临床解释很重要，而且可能为识别针对由无意义突变引起的遗传疾病的新型治疗方法提供线索。在这里，我们讨论了 NMD 可变性的现有知识，以及尽管存在 NMD 诱导特征，但某些转录本如何逃避 NMD 的机制。本文属于：RNA 周转和监控 > 周转/监控机制 RNA 在疾病与发育中的作用 > RNA 在疾病中 RNA 周转和监控 > RNA 稳定性的调控。
