Human INT6/eIF3e is required for nonsense-mediated mRNA decay.
The mammalian integration site 6 (INT6) protein has been implicated in breast carcinogenesis and characterized as the eIF3e non-core subunit of the translation initiation factor eIF3, but its role in this complex is not known. Here, we show that INT6 knockdown by RNA interference strongly inhibits nonsense-mediated messenger RNA decay (NMD), which triggers degradation of mRNAs with premature stop codons. In contrast to the eIF3b core subunit, which is required for both NMD and general translation, INT6 is only necessary for the former process. Consistent with such a role, immunoprecipitation experiments showed that INT6 co-purifies with CBP80 and the NMD factor UPF2. In addition, several transcripts known to be upregulated by UPF1 or UPF2 depletion were also found to be sensitive to INT6 suppression. From these observations, we propose that INT6, in association with eIF3, is involved in routing specific mRNAs for degradation.
Morris
Christelle
C
LBMC, UMR5239 CNRS-ENS de Lyon, IFR 128 Biosciences Lyon Gerland, 46 Allée d'Italie, 69364 Lyon cedex 07, France.
Wittmann
Jürgen
J
Jäck
Hans-Martin
HM
Jalinot
Pierre
P
D018389:Codon, Nonsense / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000172:deficiency / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D039502:Nuclear Cap-Binding Protein Complex / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D020365:RNA Helicases; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018389:Codon, Nonsense; D039621:Eukaryotic Initiation Factor-3; D039502:Nuclear Cap-Binding Protein Complex; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C468286:UPF2 protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human