Post-transcriptional control of gene expression by Adenosine and uridine-rich elements


Abstract : AU-rich elements (ARE) are major regulatory motifs found in mRNA 3’ untranslated regions. These elements modulate stability and translation of a large array of genes. The host laboratory has established the existence of ARE-mediated decay in Drosophila melanogaster and has clearly established the usefulness of this experimental model to better characterize ARE functions. Recently, we observed that presence of putative ARE in several drosophila genes induced by hypoxia and encoding key metabolic enzymes. Our preliminary experiments suggest that the AU-rich binding factor Tis11 might regulates the level of mRNA coding for Lactate Deshydrogenase (LDH), Pyruvate Deshydrogenase Kinase (PDK) and Phosphoenol-Pyruvate Carboxykinase (PEPCK). We also observed that the level of TIS11 protein in drosophila cells is modulated in hypoxia. Based on these observations we propose to investigate the molecular mechanism by which TIS11 controls the production of LDH, PDK and PEPCK in drosophila cells in an oxygen depend manner. We will determine the influence of this regulation on cell metabolism in normoxia and hypoxia and evaluate the conservation of this mechanism in mammalian cells. This project should allow a better understanding of post-transcriptionnal mechanisms affecting the regulation of key metabolic genes upon variation of oxygen concentration encountered in physiological or pathophysiological situations.
Promoteur/Supervisor : Prof. Gueydan Cyril
Email : cgueydan@ulb.ac.be
Site Web/Web site : http://www.ulb.ac.be/rech/inventaire/unites/ULB130.html
Centre de recherche/Research center : Laboratoire de Biologie moléculaire du g&eg
Faculté/Faculty : FacultĂ© des Sciences/Faculty of Sciences
Ecole doctorale/Graduate Colleges : Sciences/Science
Ecole doctorale thématique/Graduate School (French Only): Biologie Cellulaire et MolĂ©culaire, Biochimie (BCMB)



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