Objective
R-loops are long RNA/DNA hybrids naturally formed behind RNA polymerase II (Pol II) during transcription, but their persistence is a threat for genome integrity through the creation of DNA damage, leading to cancer development. However, several recent studies reported a new and exciting role for R-loops in gene expression regulation by influencing transcription termination and chromatin modification.
As mutations in several RNA processing factors have been shown to stabilize R-loop formation, we propose here to investigate the link between R-loops and co-transcriptional alternative splicing (AS) and to decipher the underlying mechanisms, a hypothesis supported by our preliminary results identifying more than 3000 splice junctions affected by decreased R-loops upon overexpression of RNase H1. The use of a specific antibody to RNA/DNA hybrids and stabilization/removal of R-loops coupled to high-throughput analysis of splicing (RNA-seq), R-loop profiling (DRIP-seq) and Pol II positioning and measurements (PRO-seq) will allow us to investigate genome-wide regulation of AS by R-loop formation. We will use particular AS events as models to elucidate the molecular mechanisms interconnecting R-loops and AS. Moreover, based on our previous expertise, we plan to study the impact of R-loops on DNA damage-induced AS alteration as a model of physiological regulation of AS by R-loops.
This project will provide new insights on AS regulation through the formation of R-loops and also on cancer progression through R-loop stabilization. Finally, this project will allow me to acquire independent thinking and scientific leadership to reach an independent academic position in France.
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.
- medical and health sciences clinical medicine oncology skin cancer
- natural sciences biological sciences genetics DNA
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences genetics genomes eukaryotic genomes
You need to log in or register to use this function
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.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
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.
MSCA-IF-EF-RI - RI – Reintegration panel
See all projects funded under this funding scheme
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) H2020-MSCA-IF-2014
See all projects funded under this callCoordinator
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.
08003 Barcelona
Spain
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.