Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.
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.
Kashima
Isao
I
Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
Yamashita
Akio
A
Izumi
Natsuko
N
Kataoka
Naoyuki
N
Morishita
Ryo
R
Hoshino
Shinichi
S
Ohno
Mutsuhito
M
Dreyfuss
Gideon
G
Ohno
Shigeo
S
D018389:Codon, Nonsense / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008666:Metalloendopeptidases; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020365:RNA Helicases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D018389:Codon, Nonsense; C489002:ETF1 protein, human; D009097:Multienzyme Complexes; D010454:Peptide Termination Factors; C406243:RBM8A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D015534:Trans-Activators; D014157:Transcription Factors; C468286:UPF2 protein, human; C026452:messenger ribonucleoprotein; C087971:peptide-chain-release factor 3; D011494:Protein Kinases; D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase; D020365:RNA Helicases; C101828:UPF1 protein, human