Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2022-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
8000 Aarhus C
Denmark
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.