Objectif .Mammalian transcriptome analysis reveals that while most of the genome is transcribed, only a minority fraction produces protein coding, messenger RNA or functional, structural RNA. Instead a substantial fraction is transcribed, often tissue specifically, into long non coding (lnc)RNA of mostly unknown function. Many lncRNA are rapidly degraded and may reflect promiscuous, non-functional transcription. However some lncRNA have important cellular functions. I reason that defining promoters and terminators of lncRNA genes will provide valuable information on which lncRNA are likely to be functional. LncRNA gene promoters often correspond to nucleosome depleted regions of protein coding gene promoters and enhancers, which generate bidirectional transcription. Regions of single-strand DNA, exposed by R-loop formation can also initiate transcription and so act as a potential source of lncRNA, as will be investigated here. Since transcription initiation of lncRNA genes appears relatively promiscuous, terminating lncRNA transcription may be of critical importance. This will prevent read-through transcription with consequent negative affects on downstream genes by transcriptional interference or the formation of overlapping transcripts leading to RNA interference effects. Consequently I will focus on transcription termination mechanisms of lncRNA genes. I will determine if known protein coding gene terminators also operate for lncRNA genes or whether many lncRNA use alternative termination mechanisms. In particular I will investigate the role of G-rich pausing elements that promote Pol II termination by forming R-loop structures on lncRNA genes. I will also investigate which classes of lncRNA genes form gene loop conformations when transcribed, as a likely identifier of more highly expressed, functional lncRNA. Overall I predict that understanding how lncRNA are synthesised will provide critical information on which lncRNA warrant scrutiny as likely functional transcripts Champ scientifique natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes 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-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Appel à propositions ERC-2013-ADG Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Contribution de l’UE € 2 499 464,00 Adresse WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Royaume-Uni Voir sur la carte Région South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Type d’activité Higher or Secondary Education Establishments Contact administratif Gill Wells (Ms.) Chercheur principal Nicholas Jarvis Proudfoot (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 THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Royaume-Uni Contribution de l’UE € 2 499 464,00 Adresse WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Voir sur la carte Région South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Type d’activité Higher or Secondary Education Establishments Contact administratif Gill Wells (Ms.) Chercheur principal Nicholas Jarvis Proudfoot (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
