Nonsense-mediated mRNA decay (NMD)

Nonsense-mediated mRNA decay (NMD) is a critical eukaryotic surveillance pathway that identifies and degrades mRNA transcripts containing premature termination codons (PTCs) [Kurosaki et al., 2019, Nature Reviews Molecular Cell Biology]. By eliminating these aberrant transcripts, NMD prevents the synthesis of potentially harmful truncated proteins that could exert dominant-negative effects or interfere with normal cellular processes [Lykke-Andersen & Jensen, 2015, Nature Reviews Molecular Cell Biology]. Beyond its quality control function, NMD also serves as a post-transcriptional regulatory mechanism for approximately 5-10% of normal physiological mRNAs, thereby influencing cell growth, differentiation, and the response to environmental stress [Nasif et al., 2018, Journal of Molecular Biology]. In many genetic diseases, such as cystic fibrosis and Duchenne muscular dystrophy, NMD degrades transcripts that might otherwise produce partially functional proteins, which can exacerbate the clinical phenotype [Holbrook et al., 2004, Nature Genetics]. Pharmacological modulation of NMD, either through the direct inhibition of NMD factors like UPF1 or through the use of read-through agents like ataluren, represents a significant therapeutic strategy to restore protein expression in disorders caused by nonsense mutations [Huang & Wilkinson, 2012, Annual Review of Genetics].

Other names

mRNA surveillanceNonsense-mediated decayNMD pathwayRNA surveillance mechanism

Inhibition of NMD core factors (e.g., UPF1, SMG1) to stabilize PTC-containing transcripts or promotion of translational read-through of premature termination codons (PTCs) to bypass NMD-mediated degradation.