Objectif In eukaryotes, almost all RNA molecules are processed at their 3’ ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases (PAPs). Recently, several new non-canonical poly(A) (ncPAPs) and poly(U) polymerases (PUPs) have been discovered that have more specific regulatory roles. In contrast to canonical ones, their functions are more diverse; some induce RNA decay while others, especially cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. Knowledge about ncPAPs and PUPs is very scarce and there are crucial questions about their functions that need to be addressed.The project has 3 parts:1) Functional analysis of FAM46 proteins, which, according to our preliminary data, constitute a new family of active poly(A) polymerases. FAM46C is frequently mutated in myelomas and mutations in its mouse orthologue cause anaemia, thus demonstrating important biological functions of this unexplored family of proteins.2) Elucidation of the functions of all known vertebrate ncPAPs and PUPs (7 previously known and 4 members of FAM46 family) using the chicken DT40 cell line as a model system. DT40 has an exceptionally high rate of homologous recombination, allowing easy gene targeting and generation of multiple knockouts that facilitate the study of proteins with overlapping functions.3) Cytoplasmic polyadenylation of dormant mRNA molecules activates translation in neurons, gametes and reticulocytes. In neurons, it occurs in axons and dendrites following synaptic stimulation while in oocytes, it is induced by progesterone. The exact impact on gene expression is not well defined due to a lack of technologies identifying cytoplasmically polyadenylated transcripts. We will develop a novel detection method for ongoing RNA polyadenylation to assess the biological significance of cytoplasmic polyadenylation. This part of the project will be developed using mouse synaptoneurosomes and then transferred to reticulocytes and possibly oocytes. Champ scientifique natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysisnatural sciencesbiological sciencesgeneticsRNA Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Appel à propositions ERC-2012-StG_20111109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil INSTYTUT BIOCHEMII I BIOFIZYKI POLSKIEJ AKADEMII NAUK Contribution de l’UE € 1 500 000,00 Adresse PAWINSKIEGO 5A 02 106 Warszawa Pologne Voir sur la carte Région Makroregion województwo mazowieckie Warszawski stołeczny Miasto Warszawa Type d’activité Research Organisations Contact administratif Piotr Zielenkiewicz (Prof.) Chercheur principal Andrzej Dziembowski (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire INSTYTUT BIOCHEMII I BIOFIZYKI POLSKIEJ AKADEMII NAUK Pologne Contribution de l’UE € 1 500 000,00 Adresse PAWINSKIEGO 5A 02 106 Warszawa Voir sur la carte Région Makroregion województwo mazowieckie Warszawski stołeczny Miasto Warszawa Type d’activité Research Organisations Contact administratif Piotr Zielenkiewicz (Prof.) Chercheur principal Andrzej Dziembowski (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée