Nonsense-Mediated mRNA Decay: Degradation of Defective Transcripts Is Only Part of the Story

Annu Rev Genet. 2015:49:339-66. doi: 10.1146/annurev-genet-112414-054639. Epub 2015 Oct 2.


Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that monitors cytoplasmic mRNA translation and targets mRNAs undergoing premature translation termination for rapid degradation. From yeasts to humans, activation of NMD requires the function of the three conserved Upf factors: Upf1, Upf2, and Upf3. Here, we summarize the progress in our understanding of the molecular mechanisms of NMD in several model systems and discuss recent experiments that address the roles of Upf1, the principal regulator of NMD, in the initial targeting and final degradation of NMD-susceptible mRNAs. We propose a unified model for NMD in which the Upf factors provide several functions during premature termination, including the stimulation of release factor activity and the dissociation and recycling of ribosomal subunits. In this model, the ultimate degradation of the mRNA is the last step in a complex premature termination process.

Keywords: Upf proteins; quality control; ribosome dissociation; translation termination.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Mammals
  • Nonsense Mediated mRNA Decay / physiology*
  • Peptide Chain Termination, Translational
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Serine-Threonine Kinases
  • RNA Helicases
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • RNA-Binding Proteins
  • Trans-Activators
  • Transcription Factors
  • UPF2 protein, human
  • UPF3A protein, human
  • Protein Serine-Threonine Kinases
  • SMG1 protein, human
  • RNA Helicases
  • UPF1 protein, human