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This article is part of the Research Topic

RNA Regulation in Development and Disease

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00254

Differential regulation of the three eukaryotic mRNA translation initiation factor (eIF) 4Gs by the proteasome

Amandine Alard1, Catherine Marboeuf1,  Bertrand Fabre1, Christine Jean1,  Yvan Martineau1,  Frédéric Lopez1, Patrice Vende2,  Didier Poncet2, Robert J. Schneider3,  Corinne Bousquet1 and  Stéphane Pyronnet1*
  • 1Institut National de la Santé et de la Recherche Médicale (INSERM), France
  • 2Centre National de la Recherche Scientifique (CNRS), France
  • 3New York University, United States

The 4G family of eukaryotic mRNA translation initiation factors is composed of three members (eIF4GI, eIF4GII and DAP5). Their specific roles in translation initiation are under intense investigations, but how their respective intracellular amounts are controlled remains poorly understood. Here we show that eIF4GI and eIF4GII exhibit much shorter half-lives than that of DAP5. Both eIF4GI and eIF4GII proteins, but not DAP5, contain PEST motifs in their N-termini conserved across the animal kingdom and sufficient for targeting them to the proteasome. Under normal conditions, eIF4GI and eIF4GII are protected from proteasomal destruction through binding to the detoxifying enzyme NQO1 (NAD(P)H:quinone oxidoreductase). However, when cells are exposed to oxidative stress both eIF4GI and eIF4GII, but not DAP5, are degraded by the proteasome in a PEST-dependent manner, and cell viability is more compromised upon silencing of DAP5. These findings indicate that the three eIF4G proteins are differentially regulated by the proteasome and that persistent DAP5 plays a role in cell survival upon oxidative stress.

Keywords: mRNA translation, eIF4G, DAP5, Pest, NQO1, Nrf2, Proteasome, Oxidative Stress

Received: 07 Aug 2018; Accepted: 07 Mar 2019.

Edited by:

Maritza Jaramillo, Institute Armand Frappier, National Institute of Scientific Research, University of Quebec, Canada

Reviewed by:

Motoaki Wakiyama, RIKEN, Japan
Jerry Pelletier, McGill University, Canada  

Copyright: © 2019 Alard, Marboeuf, Fabre, Jean, Martineau, Lopez, Vende, Poncet, Schneider, Bousquet and Pyronnet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Stéphane Pyronnet, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France, stephane.pyronnet@inserm.fr