Description du projet
Étude de la régulation de l’expression génétique
Les cellules régulent fortement l’expression des gènes dans le temps et l’espace afin de garantir que les bonnes protéines sont produites au moment et à l’endroit requis. La régulation de l’expression génétique est un processus complexe qui implique une interaction multipartite d’éléments régulateurs, tels que les facteurs de transcription, les modifications épigénétiques et les ARN non-codants. Le projet moreRNA, financé par le Conseil européen de la recherche, se concentrera sur la maturation des microARN et sur l’impact des événements de méthylation directe de l’ARN sur l’expression génétique. Les chercheurs feront appel à des techniques de biologie moléculaire et cellulaire pour analyser le rôle de la voie de méthylation dans la régulation des ARN codants et non-codants. De manière générale, le projet mettra en lumière des facteurs d’expression génétique et des voies de régulation jusqu’ici inconnus.
Objectif
Coding and non-coding RNAs are regulated at numerous levels. For example, microRNA (miRNA) expression can be influenced at various steps of biosynthesis. Furthermore, it has been reported that direct RNA methylation events can also affect gene expression in many different organisms and systems. The aim of this project is to identify and characterize factors that affect the maturation of miRNAs. We will employ biochemical pull down assays to isolate specific binding partners of different miRNA species. We will analyze the physiological role of these factors using molecular or cell biological approaches. Molecular details of pre-miRNA-protein interactions will be investigated by x-ray crystallography. In addition, we will decipher the role of the m6A methylation pathway on the regulation of coding and non-coding RNAs. Writers, readers and erasers of this modification have been identified. However, not much is known about the composition of specific protein complexes as well as the atomic structure of these factors. Thus, we will functionally and structurally characterize known and putative novel factors of the m6A methylation pathway in human cells. Furthermore, using our biochemical pull down approach employed for the identification of pre-miRNA processing factors, we will identify reader proteins of several types of RNA modification that have not been investigated so far. The proposed project will elucidate the regulation of gene expression by small RNAs or direct RNA methylation and will add so far unknown components to these important regulatory pathways.
Champ scientifique
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesgeneticsgenomes
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
93053 Regensburg
Allemagne