The broader sense of nonsense

The term 'nonsense-mediated mRNA decay' (NMD) was initially coined to describe the translation-dependent degradation of mRNAs harboring premature termination codons (PTCs), but it is meanwhile known that NMD also targets many canonical mRNAs with numerous biological implications. The molecular mechanisms deter-mining on which RNAs NMD ensues are only partially understood. Considering the broad range of NMD-sensitive RNAs and the variable degrees of their degrada-tion, we highlight here the hallmarks of mammalian NMD and point out open ques-tions. We review the links between NMD and disease by summarizing the role of NMD in cancer, neurodegeneration, and viral infections. Finally, we describe strate-gies to modulate NMD activity and specificity as potential therapeutic ap-proaches for various diseases.

Automated summary

The article reviews the important role of NMD in mRNA degradation, discusses its impact on various diseases, and proposes strategies to modulate NMD as potential therapeutic approaches.