Description du projet
Disséquer la biogénèse de l’ARN polymérase
Le génome humain contient environ 20 000 gènes codant pour des protéines. Ceux-ci sont transcrits en ARNm par l’enzyme ARN polymérase II (RNAPII), un complexe multiprotéique composé de 12 sous-unités. La régulation et l’assemblage de RNAPII sont essentiels à l’expression correcte des gènes. Financé par le programme Actions Marie Skłodowska-Curie, le projet RNAPII biogenesis étudiera l’abondance, le transport et le temps d’assemblage des enzymes, offrant ainsi une vision globale de la biogénèse de RNAPII. Les chercheurs chercheront à découvrir si les sous-unités de RNAPII dans les cellules eucaryotes s’assemblent de manière co-traductionnelle. Collectivement, les travaux de RNAPII biogenesis alimenteront les recherches futures sur son exploitation potentielle en tant que cible anticancéreuse.
Objectif
Cellular diversity in eukaryotic organisms is obtained through differential regulation of transcription, which is therefore a heavily studied step in gene expression. Protein-coding genes are transcribed by RNA polymerase II (RNAPII), an enzyme consisting of twelve subunits. Recently, work from my host lab, the Svejstrup lab, has suggested that depleting the number of fully assembled RNAPII molecules in the cell, through degradation of its main catalytic subunit RPB1, is crucial for achieving transcription recovery after DNA damage. This finding underscores the importance of understanding how RNAPII levels are regulated. Therefore, in this proposal I aim to gain insight into the mechanisms influencing RNAPII abundance, by studying RPB1 mRNA and protein levels, RNAPII assembly, and RNAPII transport in human cells. Specifically, I will leverage my background in RNA biology and bioinformatics analysis to identify RNA-binding proteins interacting with the 3’UTR of RPB1, and study their role in regulating RPB1 mRNA turnover and translation efficiency. Moreover, using state-of-the-art selective ribosomal profiling techniques, I will determine whether RNAPII is assembled co-translationally, as was recently proposed to be the mechanism of assembly for most multi-subunit complexes in eukaryotes. Finally, I will perform a CRISPR-Cas9 screen to identify novel factors that mediate RNAPII nuclear import. Together, this proposal will elucidate the biogenesis of RNAPII, which is crucial for a better understanding of transcription regulation. The proposed experiments will enhance my postdoctoral training by broadening my conceptual and technical skills and will provide data and tools to start my own laboratory in the future. Ultimately, these findings might also have therapeutic implications, as RNAPII is one of the targets being investigated for cancer treatments.
Champ scientifique
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
MSCA-PF - MSCA-PFCoordinateur
1165 Kobenhavn
Danemark