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RNAPII biogenesis

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Regulating RNAPII levels: gaining insight into the translation, assembly and tra...

Regulating RNAPII levels: gaining insight into the translation, assembly and transport of RNAPII subunits. 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 (RNAP... ver más

31/08/2025

UCPH

215K€

Presupuesto del proyecto: 215K€

Líder del proyecto

KOBENHAVNS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-07-18

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021

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01-12-2024: REDES En las últimas 48 horas el Organismo REDES ha otorgado 1337 concesiones

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Duración del proyecto: 37 meses Fecha Inicio: 2022-07-18
Fecha Fin: 2025-08-31

Líder del proyecto

KOBENHAVNS UNIVERSITET

TRL 4-5

Presupuesto del proyecto 215K€

Descripción del proyecto 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.

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