NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA.
Nonsense-mediated messenger RNA decay (NMD) generally degrades mRNAs that prematurely terminate translation as a means of quality control. NMD in mammalian cells targets newly spliced mRNA that is bound by the cap-binding protein heterodimer CBP80/20 and one or more post-splicing exon junction complexes during a pioneer round of translation. NMD targets mRNA that initiates translation using the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES), therefore NMD might target not only CBP80/20-bound mRNA but also its remodelled product, eIF4E-bound mRNA. Here, we provide evidence that NMD triggered by translation initiation at the EMCV IRES, similar to NMD triggered by translation initiation at an mRNA cap, targets CBP80/20-bound mRNA but does not detectably target eIF4E-bound mRNA. We show that EMCV IRES-initiated translation undergoes a CBP80/20-associated pioneer round of translation that results in CBP80/20-dependent and Upf factor-dependent NMD when translation terminates prematurely.
Woeller
Collynn F
CF
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA.
Gaspari
Martina
M
Isken
Olaf
O
Maquat
Lynne E
LE
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D018389:Codon, Nonsense / Q000378:metabolism*; D019281:Dimerization; D004686:Encephalomyocarditis virus / Q000235:genetics*; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D039502:Nuclear Cap-Binding Protein Complex / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D020365:RNA Helicases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018389:Codon, Nonsense; D039561:Eukaryotic Initiation Factor-4E; D039502:Nuclear Cap-Binding Protein Complex; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C468286:UPF2 protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human