Objectif Transcription, the copying of DNA into RNA, is the first step in the realisation of genetic information. RNA is either directly used by the cell or decoded into proteins during translation. The accuracy of transcription is thus essential for proper functioning of the cell. In all living organisms transcription is performed by multisubunit RNA polymerases, enzymes that are highly conserved in evolution from bacteria to humans. Surprisingly, the mechanisms that ensure accuracy of transcription remain largely unknown. Recently I discovered a novel mechanism of transcriptional proofreading used by bacterial RNA polymerase. I showed that the RNA transcript itself assists RNA polymerase in identifying and correcting mistakes. This discovery led to the hypothesis that this transcript-assisted proofreading is the universal mechanism of transcriptional error correction in all three domains of life. In this proposal we will investigate this hypothesis and search for other mechanisms of transcriptional proofreading used by bacterial, archaeal, and three eukaryotic RNA polymerases. For the first time experimental systems will be built for the simultaneous investigation of transcription elongation complexes formed by bacterial, archaeal and eukaryotic RNA polymerases I, II and III, which will be used to elucidate the mechanisms of error correction used by these RNA polymerases. Using molecular modelling, directed mutagenesis and in vivo screenings we will investigate the impact of these proofreading mechanisms on the total fidelity of transcription in vitro and in vivo. Experimental systems built in this research may be of use for screening of potential antibacterial and antifungal drugs taking advantage of the simultaneous investigation of RNA polymerases from all domains of Life. This research may also have potential applications in drug design by providing new targets for antibiotics. Champ scientifique natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicinemedicinal chemistrymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Mots‑clés RNA polymerase Transcription elongation complex fidelity proofreading 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-2007-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil UNIVERSITY OF NEWCASTLE UPON TYNE Contribution de l’UE € 1 149 831,00 Adresse KINGS GATE NE1 7RU Newcastle Upon Tyne Royaume-Uni Voir sur la carte Région North East (England) Northumberland and Tyne and Wear Tyneside Type d’activité Higher or Secondary Education Establishments Chercheur principal Nikolay Zenkin (Dr) Contact administratif Amanda Gregory (Dr.) 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 UNIVERSITY OF NEWCASTLE UPON TYNE Royaume-Uni Contribution de l’UE € 1 149 831,00 Adresse KINGS GATE NE1 7RU Newcastle Upon Tyne Voir sur la carte Région North East (England) Northumberland and Tyne and Wear Tyneside Type d’activité Higher or Secondary Education Establishments Chercheur principal Nikolay Zenkin (Dr) Contact administratif Amanda Gregory (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
