Background

One-third of inherited human diseases are caused by mutated mRNAs harboring premature termination codons (PTCs). Nonsense-mediated mRNA decay (NMD) is a critical cellular surveillance mechanism that recognizes and eliminates aberrant RNAs containing PTC. NMD plays an important role in cell cycle regulation, cell viability, and DNA damage response, while also serving as a barrier to virus infection. Disturbance of this control mechanism can lead to pathologies, including neurological disorders, immune diseases and cancers. Data estimate that ~22% of disease-causing PTCs are predicted to be insensitive to NMD. Therefore, controlling NMD activity is an attractive approach to developing novel therapeutics for many human diseases.