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RLOOP-AS

Interconnection between R-loops and co-transcriptional alternative splicing

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

RLOOP-AS project word cloud

Explore the words cloud of the RLOOP-AS project. It provides you a very rough idea of what is the project "RLOOP-AS" about.

rna 3000 coupled seq positioning co naturally formed removal gene expertise integrity hypothesis molecular splice throughput shown model alteration acquire france termination polymerase academic stabilization independent influencing thinking me reported leadership elucidate decreased models h1 alternative cancer profiling chromatin stabilize events junctions damage scientific threat regulation pro progression position persistence physiological decipher hybrids plan creation rnase underlying loop insights dna genome overexpression expression drip antibody modification link mutations splicing transcriptional pol transcription loops preliminary mechanisms interconnecting

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 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.	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

List of publications.
year	authors and title	journal	last update
2017	Manuel J. MuÃ±oz, NicolÃ¡s Nieto Moreno, Luciana E. Giono, AdriÃ¡n E. Cambindo Botto, Gwendal Dujardin, Giulia Bastianello, Stefania Lavore, Antonio Torres-MÃ©ndez, 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, NicolÃ¡s Nieto Moreno, AdriÃ¡n E. Cambindo Botto, Gwendal Dujardin, Manuel J. MuÃ±oz, 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, Ã‰lisabeth Daguenet, Delphine G. Bernard, Marion Flodrops, StÃ©phanie Durand, AurÃ©lie Chauveau, Flaria El Khoury, Catherine Le Jossic-Corcos, Laurent Corcos Lâ€™Ã©pissage des ARNÂ prÃ©-messagersÂ : quand le splicÃ©osome perd pied published pages: 1103-1110, ISSN: 0767-0974, DOI: 10.1051/medsci/20163212014	mÃ©decine/sciences 32/12	2019-07-24

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