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Human INT6/eIF3e is required for nonsense‐mediated mRNA decay

Christelle Morris, Jürgen Wittmann, Hans‐Martin Jäck, Pierre Jalinot

Author Affiliations

  1. Christelle Morris1,
  2. Jürgen Wittmann2,
  3. Hans‐Martin Jäck2 and
  4. Pierre Jalinot*,1
  1. 1 LBMC, UMR5239 CNRS‐ENS de Lyon, IFR 128 Biosciences Lyon Gerland, 46 Allée d'Italie, 69364, Lyon, cedex 07, France
  2. 2 Division of Molecular Immunology, Department of Internal Medicine 3, Nikolaus‐Fiebiger‐Center, University of Erlangen‐Nürnberg, Gluckstrasse 6, D‐91054, Erlangen, Germany
  1. *Corresponding author. Tel: +33 4 7272 8563; Fax: +33 4 7272 8080; E-mail: pjalinot{at}ens-lyon.fr
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Abstract

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.

  • Received October 19, 2006.
  • Revision received February 20, 2007.
  • Accepted March 1, 2007.
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