eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay

Nat Struct Mol Biol. 2004 Apr;11(4):346-51. doi: 10.1038/nsmb750. Epub 2004 Mar 21.


The exon junction complex (EJC), a set of proteins deposited on mRNAs as a consequence of pre-mRNA splicing, is a key effector of downstream mRNA metabolism. We have identified eIF4AIII, a member of the eukaryotic translation initiation factor 4A family of RNA helicases (also known as DExH/D box proteins), as a novel EJC core component. Crosslinking and antibody inhibition studies suggest that eIF4AIII constitutes at least part of the platform anchoring other EJC components to spliced mRNAs. A nucleocytoplasmic shuttling protein, eIF4AIII associates in vitro and in vivo with two other EJC core factors, Y14 and Magoh. In mammalian cells, eIF4AIII is essential for nonsense-mediated mRNA decay (NMD). Finally, a model is proposed by which eIF4AIII represents a new functional class of DExH/D box proteins that act as RNA clamps or 'place holders' for the sequence-independent attachment of additional factors to RNAs.

Publication types

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

MeSH terms

  • Binding Sites
  • Codon, Nonsense
  • Eukaryotic Initiation Factor-4A / metabolism*
  • Exons / genetics*
  • Genes, Reporter
  • Glutathione Transferase / genetics
  • Humans
  • Kinetics
  • Polymerase Chain Reaction
  • RNA Splicing*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Recombinant Fusion Proteins / metabolism


  • Codon, Nonsense
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Glutathione Transferase
  • Eukaryotic Initiation Factor-4A