Projet ANR-07-BLAN-0093 – REGARD : REGULATION OF mRNA LEVELS THROUGH THEIR DECAY (REGulation du niveau des ARNm par la Degradation : REGARD)
Programme : Blanc (BLANC) 2007
Année de financement : 2007
Coordinateur du projet : Monsieur Bertrand Séraphin (CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET EN MEDECINE - CERBM)
Partenaires : CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET EN MEDECINE
Montant : 279000.0 euros
Date de début : 2007
Durée : 36 mois
Résumé : Regulation of gene expression is a complex process that is essential to allow cells to adapt to changing conditions. Degradation of messenger RNAs plays an important role in the control of gene expression, but the mechanisms involved remains poorly understood. A specific problem associated with analysis of this process is the existence of several mRNA decay pathways that act concomitantly. In this situation, it is often difficult, or even impossible, to establish how a given mRNA is degraded. We propose to develop a new method to analyse mRNA degradation. This strategy will permit to detect quantitatively degradation intermediates specific for each pathways. We will thus be able to evaluate the fraction of a given mRNA being degraded through a given pathway at a given time-point. This strategy will thus be particularly well adapted to the analysis of regulation of mRNA decay. We propose to apply this new strategy to the analysis of two regulators: ataxin 2 and BTG/Tob family members. Interestingly, these factors are implicated in human diseases. Our studies will include the research of protein partners to these factors through proteomic analysis, the identification of target mRNAs, and the dissection of their mechanisms of action. Interestingly, in the case of BTG/Tob factors, we have accumulated data suggesting that the regulation of mRNA decay may involve protein post-translational modification through methylation. -  In summary, this project will allow the development of a new strategy for the analysis of mRNA decay. This strategy, in combination with a variety of complementary studies, will be applied to allow the understanding of the mechanism of action of two factors involved in mRNA decay regulation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             ...