PervasiveTranscript
Financiado
Controlling Pervasive Transcription
The human genome is pervasively transcribed, producing RNA from ~ 80-90% of its DNA, yet only a small fraction of transcripts result in the generation of functional RNAs. Instead, the majority of transcription initiation events ar...
The human genome is pervasively transcribed, producing RNA from ~ 80-90% of its DNA, yet only a small fraction of transcripts result in the generation of functional RNAs. Instead, the majority of transcription initiation events are prematurely terminated and the resulting RNA is targeted by decay pathways. How cells ‘determine’ which RNAs to degrade vs. which to prepare for functional tasks, is a central question. Interestingly, new data from my host laboratory, that motivates this application, suggest that non-productive transcription events are correlated with low transcription initiation levels; i.e. lowly transcribed RNAs appear to be more susceptible to early termination and ensuing rapid degradation. Transcription termination in these instances is conducted by either Integrator (INT) complex or components interacting with ARS2 transcription termination factor. In the present project, I will investigate the mechanisms underlying this relationship, which could possibly rationalize how cells keep their spurious transcription under control. Considering the association of INT and ARS2 mutations with cancer and neurological diseases, my results might also pave the way for therapeutic interventions.
Previous approaches utilizing targeted transcription repression/activation by CRISPRi/a approach are based on absolute On/Off transcription from the selected loci without the ability to fine-tune the transcription at a predicted level. Here, I will utilise newly reported mismatch guide RNA/CRISPR-dCas9 to manipulate initiation to defined levels and hereby establish a tuneable system to assay the fate of RNAs expressed from weaker vs. stronger promoters. I will then exploit this system to address the molecular mechanism, dictating genome control based on transcription initiation levels.
The findings of my project will be of interest to many disciplines of the scientific community in that it might help explain how genome expression is sorted at a higher order level.
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Duración del proyecto: 40 meses
Fecha Inicio: 2023-04-26
Fecha Fin: 2026-08-31
Fecha Fin: 2026-08-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-26
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2022-PF-01-01:
MSCA Postdoctoral Fellowships 2022
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
215K€
Líder del proyecto
AARHUS UNIVERSITET
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5