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V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors

Oncogene volume 33, pages 1581–1589 (2014)Cite this article

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Abstract

The v-erbA oncogene transforms chicken erythrocytic progenitors (T2EC) by blocking their differentiation and freezing them in a state of self-renewal. Transcriptomes of T2EC, expressing either v-erbA or a non-transforming form of v-erbA (S61G), were compared using serial analysis of gene expression and some, but not all, mRNA-encoding ribosomal proteins were seen to be affected by v-erbA. These results suggest that this oncogene could modulate the composition of ribosomes. In the present study, we demonstrate, using two-dimensional difference in gel electrophoresis, that v-erbA-expressing cells have a lower amount of RPL11 associated with the ribosomes. The presence of ribosomes devoid of RPL11 in v-erbA-expressing cells was further confirmed by immunoprecipitation. In order to assess the possible impact of these specialized ribosomes on the translational activity, we analyzed proteomes of either v-erbA or S61G-expressing cells using 2D/mass spectrometry, and identified nine proteins present in differing amounts within these cells. Among these proteins, we focused on HSP70 because of its involvement in erythroid differentiation. Our results indicate that, in v-erbA-expressing cells, hsp70 is not only transcribed but also translated more efficiently, as shown by polyribosome fractionation experiments. We demonstrate here, for the first time, the existence of ribosomes with different protein components, notably ribosomes devoid of RPL11, and a regulation of mRNA translation depending on v-erbA oncogene expression.

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Acknowledgements

We thank Dr Stephanie Gobert-Gosse (Universite Claude Bernard Lyon 1, Villeurbanne, France) for her expert advice on the two-dimensional electrophoresis experiments and Clément Soleilhavoup for his technical help in the analysis of total mRNA levels by RT–qPCR. This work received support from grants from Association pour la Recherche contre le Cancer, Ligue contre le Cancer (Comité Départemental du Rhône), Société Française d’Hématologie (SFH), Région Rhône-Alpes, Université Claude Bernard Lyon 1 (UCBL1) and Centre National de la Recherche Scientifique (CNRS).

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Authors and Affiliations

  1. Centre de Génétique et de Physiologie Moléculaire et Cellulaire, CNRS UMR 5534, Université de Lyon, Université Lyon1, Villeurbanne Cedex, France

    A T Nguyen-Lefebvre, G Leprun, V Morin, J Viñuelas, J-J Madjar, O Gandrillon & S Gonin-Giraud

  2. CEA, IRTSV, Laboratoire Biologie à Grande Echelle, Grenoble, France

    Y Couté

  3. INSERM, U1038, Grenoble, France

    Y Couté

  4. Université Joseph Fourier, Grenoble 1, Grenoble, France

    Y Couté

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  1. A T Nguyen-Lefebvre
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Correspondence to S Gonin-Giraud.

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Nguyen-Lefebvre, A., Leprun, G., Morin, V. et al. V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors. Oncogene 33, 1581–1589 (2014). https://doi.org/10.1038/onc.2013.93

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