Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay

Genes Dev. 2006 Feb 1;20(3):355-67. doi: 10.1101/gad.1389006.

Abstract

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNA containing premature termination codons (PTCs). In mammalian cells, recognition of PTCs requires translation and depends on the presence on the mRNA with the splicing-dependent exon junction complex (EJC). While it is known that a key event in the triggering of NMD is phosphorylation of the trans-acting factor, Upf1, by SMG-1, the relationship between Upf1 phosphorylation and PTC recognition remains undetermined. Here we show that SMG-1 binds to the mRNA-associated components of the EJC, Upf2, Upf3b, eIF4A3, Magoh, and Y14. Further, we describe a novel complex that contains the NMD factors SMG-1 and Upf1, and the translation termination release factors eRF1 and eRF3 (SURF). Importantly, an association between SURF and the EJC is required for SMG-1-mediated Upf1 phosphorylation and NMD. Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon, Nonsense / genetics
  • Codon, Nonsense / metabolism*
  • Exons / genetics
  • Exons / physiology
  • HeLa Cells
  • Humans
  • Metalloendopeptidases
  • Models, Biological
  • Multienzyme Complexes / metabolism*
  • Peptide Termination Factors / genetics
  • Peptide Termination Factors / metabolism*
  • Phosphorylation
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein Biosynthesis / genetics
  • Protein Biosynthesis / physiology
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA Helicases
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transfection

Substances

  • Codon, Nonsense
  • ETF1 protein, human
  • Multienzyme Complexes
  • Peptide Termination Factors
  • RBM8A protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • Trans-Activators
  • Transcription Factors
  • UPF2 protein, human
  • messenger ribonucleoprotein
  • peptide-chain-release factor 3
  • Protein Kinases
  • Metalloendopeptidases
  • O-sialoglycoprotein endopeptidase
  • RNA Helicases
  • UPF1 protein, human