Activation of a GPCR leads to eIF4G phosphorylation at the 5′ cap and to IRES-dependent translation

    1. Pascale Crepieux1,2,3,4
    1. 1UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
      2Group «Biology and Bioinformatics of Signaling Systems (BIOS)», CNRS, UMR7247, F-37380 Nouzilly, France
      3Université François Rabelais, F-37041 Tours, France
      4IFCE, F-37380 Nouzilly, France
      5Université Pierre et Marie Curie, University of Paris VI, CNRS, UMR 7150 Mer et Santé, Equipe Traduction, Cycle Cellulaire, et Développement, Station Biologique de Roscoff, F-29239 Roscoff, France
      6Université Européenne de Bretagne, F-29239 Roscoff, France
      7Bioinformatics Group, Department of Computer Science, University of Freiburg, Freiburg, Germany
    1. Correspondence should be addressed to P Crépieux; Email: Pascale.Crepieux{at}


    The control of mRNA translation has been mainly explored in response to activated tyrosine kinase receptors. In contrast, mechanistic details on the translational machinery are far less available in the case of ligand-bound G protein-coupled receptors (GPCRs). In this study, using the FSH receptor (FSH-R) as a model receptor, we demonstrate that part of the translational regulations occurs by phosphorylation of the translation pre-initiation complex scaffold protein, eukaryotic initiation factor 4G (eIF4G), in HEK293 cells stably expressing the FSH-R. This phosphorylation event occurred when eIF4G was bound to the mRNA 5′ cap, and probably involves mammalian target of rapamycin. This regulation might contribute to cap-dependent translation in response to FSH. The cap-binding protein eIF4E also had its phosphorylation level enhanced upon FSH stimulation. We also show that FSH-induced signaling not only led to cap-dependent translation but also to internal ribosome entry site (IRES)-dependent translation of some mRNA. These data add detailed information on the molecular bases underlying the regulation of selective mRNA translation by a GPCR, and a topological model recapitulating these mechanisms is proposed.

    • Revision received 21 March 2014
    • Accepted 28 March 2014
    • Made available online as an Accepted Preprint 7 April 2014
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