The Nonsense-Mediated Decay RNA Surveillance Pathway

Annu Rev Biochem. 2007;76:51-74. doi: 10.1146/annurev.biochem.76.050106.093909.

Abstract

Nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a "pioneer" round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC.

Publication types

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

MeSH terms

  • Animals
  • Codon
  • Exons
  • Humans
  • Multiprotein Complexes
  • Mutation, Missense*
  • Protein Biosynthesis
  • RNA Helicases
  • RNA Splicing
  • RNA Stability*
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • RNA-Binding Proteins / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism

Substances

  • Codon
  • Multiprotein Complexes
  • RNA, Messenger
  • RNA-Binding Proteins
  • Trans-Activators
  • Transcription Factors
  • UPF2 protein, human
  • UPF3A protein, human
  • RNA Helicases
  • UPF1 protein, human