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Human INT6/eIF3e is required for nonsense‐mediated mRNA decay
Author(s) -
Morris Christelle,
Wittmann Jürgen,
Jäck HansMartin,
Jalinot Pierre
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400955
Subject(s) - nonsense mediated decay , biology , initiation factor , eukaryotic translation , messenger rna , immunoprecipitation , protein subunit , eukaryotic initiation factor , gene knockdown , translation (biology) , microbiology and biotechnology , ran , rna , genetics , gene , rna splicing
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.