The broader sense of nonsense

Trends Biochem Sci. 2022 Nov;47(11):921-935. doi: 10.1016/j.tibs.2022.06.003. Epub 2022 Jun 29.


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 determining on which RNAs NMD ensues are only partially understood. Considering the broad range of NMD-sensitive RNAs and the variable degrees of their degradation, we highlight here the hallmarks of mammalian NMD and point out open questions. We review the links between NMD and disease by summarizing the role of NMD in cancer, neurodegeneration, and viral infections. Finally, we describe strategies to modulate NMD activity and specificity as potential therapeutic approaches for various diseases.

Keywords: NMD; gene expression regulation; genetic diseases; mRNA turnover; nonsense mutations; nonsense-mediated mRNA decay.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Codon, Nonsense*
  • Mammals
  • Nonsense Mediated mRNA Decay*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Codon, Nonsense
  • RNA, Messenger