Organizing principles of mammalian nonsense-mediated mRNA decay

Annu Rev Genet. 2013;47:139-65. doi: 10.1146/annurev-genet-111212-133424.


Cells use messenger RNAs (mRNAs) to ensure the accurate dissemination of genetic information encoded by DNA. Given that mRNAs largely direct the synthesis of a critical effector of cellular phenotype, i.e., proteins, tight regulation of both the quality and quantity of mRNA is a prerequisite for effective cellular homeostasis. Here, we review nonsense-mediated mRNA decay (NMD), which is the best-characterized posttranscriptional quality control mechanism that cells have evolved in their cytoplasm to ensure transcriptome fidelity. We use protein quality control as a conceptual framework to organize what is known about NMD, highlighting overarching similarities between these two polymer quality control pathways, where the protein quality control and NMD pathways intersect, and how protein quality control can suggest new avenues for research into mRNA quality control.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Cell Nucleus / metabolism
  • Codon, Nonsense / genetics
  • Exons / genetics
  • Forecasting
  • Gene Expression Regulation*
  • Gene Expression Regulation, Viral
  • Genetic Diseases, Inborn / genetics
  • Humans
  • Mammals / genetics*
  • Models, Genetic
  • Nonsense Mediated mRNA Decay / genetics*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Folding
  • Protein Processing, Post-Translational / genetics
  • RNA, Messenger / genetics*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Ubiquitination
  • Viral Proteins / genetics


  • 3' Untranslated Regions
  • Codon, Nonsense
  • RNA, Messenger
  • Ribonucleoproteins
  • Viral Proteins
  • messenger ribonucleoprotein
  • Proteasome Endopeptidase Complex