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RLOOP-AS

Interconnection between R-loops and co-transcriptional alternative splicing

Total Cost €

0

EC-Contrib. €

0

Partnership

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Project "RLOOP-AS" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO CENTRE DE REGULACIO GENOMICA 

Organization address
address: CARRER DOCTOR AIGUADER 88
city: BARCELONA
postcode: 8003
website: www.crg.es

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Project website http://www.crg.eu/en/juan_valcarcel
 Total cost 170˙121 €
 EC max contribution 170˙121 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-RI
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2017-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO CENTRE DE REGULACIO GENOMICA ES (BARCELONA) coordinator 170˙121.00

Map

 Project 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.

 Publications

year authors and title journal last update
List of publications.
2017 Manuel J. Muñoz, Nicolás Nieto Moreno, Luciana E. Giono, Adrián E. Cambindo Botto, Gwendal Dujardin, Giulia Bastianello, Stefania Lavore, Antonio Torres-Méndez, Carlos F.M. Menck, Benjamin J. Blencowe, Manuel Irimia, Marco Foiani, Alberto R. Kornblihtt
Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation
published pages: 2868-2879, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.02.066
Cell Reports 18/12 2019-07-24
2015 E. Daguenet, G. Dujardin, J. Valcarcel
The pathogenicity of splicing defects: mechanistic insights into pre-mRNA processing inform novel therapeutic approaches
published pages: 1640-1655, ISSN: 1469-221X, DOI: 10.15252/embr.201541116
EMBO reports 16/12 2019-07-24
2016 Luciana E. Giono, Nicolás Nieto Moreno, Adrián E. Cambindo Botto, Gwendal Dujardin, Manuel J. Muñoz, Alberto R. Kornblihtt
The RNA Response to DNA Damage
published pages: 2636-2651, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2016.03.004
Journal of Molecular Biology 428/12 2019-07-24
2016 Gwendal Dujardin, Élisabeth Daguenet, Delphine G. Bernard, Marion Flodrops, Stéphanie Durand, Aurélie Chauveau, Flaria El Khoury, Catherine Le Jossic-Corcos, Laurent Corcos
L’épissage des ARN pré-messagers : quand le splicéosome perd pied
published pages: 1103-1110, ISSN: 0767-0974, DOI: 10.1051/medsci/20163212014
médecine/sciences 32/12 2019-07-24

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