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MASCP SIGNED

Mechanisms of alternative pre-mRNA splicing regulation in cancer and pluripotent cells

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

MASCP project word cloud

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

integration progression promotes carry prevalent logic poorly pluripotency opportunity gene anti equivalent modulate interactions cellular precursors regulator map occurrence basis maps stem sequences reveal functional contributes cells discover core governing expands event ips evidenced area relevance splicing differentiation despite mechanisms programs coding deregulation exhaustively assays spliceosome form positional trigger cell prevalence layer line network molecular tumor mutations unweave combine technologies unresolved drugs questions genetic biochemical systematic genomes essentially mechanistic rna underlying regulatory messenger capacity cancer proliferation progress circuits alternative eukaryotic regulation pluripotent frequent contribution unprecedented

Project "MASCP" 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]
Total cost	2˙159˙574 €
EC max contribution	2˙159˙574 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2014-ADG
Funding Scheme	ERC-ADG
Starting year	2015
Duration (year-month-day)	from 2015-10-01 to 2020-09-30

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	2˙159˙574.00

Map

Project objective

Alternative splicing of messenger RNA precursors is a prevalent form of gene regulation that greatly expands the coding capacity and regulatory opportunities of higher eukaryotic genomes. It contributes to cell differentiation and pluripotency and its deregulation promotes cancer progression, as evidenced by the frequent occurrence of cancer-associated mutations in splicing factors, which are also targets of anti-tumor drugs. Despite its prevalence and relevance, the underlying mechanisms of regulation remain poorly understood. This proposal aims to develop and apply systematic approaches that can allow us to carry out the equivalent of genetic analysis of splicing regulation in cancer and pluripotent cells. These technologies can help to unweave the complex network of functional interactions within the spliceosome and of the spliceosome with regulatory factors, exhaustively map the contribution of regulatory sequences and be used to investigate, with unprecedented detail, mechanisms of regulation for essentially any regulator or alternative splicing event operating in a particular cell line. Such approaches can offer a unique opportunity to address key unresolved mechanistic questions, including the molecular basis for positional effects of splicing regulatory factors (RNA Maps), the regulatory potential of the core spliceosome and the integration of alternative splicing with other cell regulatory programs. We will combine these approaches with biochemical and cellular assays to investigate detailed mechanisms of regulation relevant for the control of cell proliferation and/or pluripotency in cancer and induced pluripotent stem (iPS) cells. Progress in this area can contribute to reveal the molecular logic governing a key layer of gene regulation and has the potential to discover novel factors and regulatory circuits that trigger or modulate cell growth, differentiation and cancer progression.

Publications

List of publications.
year	authors and title	journal	last update
2016	Mourao, A., Bonnal, S., Warner, L., Soni, K., BordonnÃ©, R., ValcÃ¡rcel, J. and Sattler, M. * * Co-corresponding authors* Structural basis for the recognition of proline-rich motifs in spliceosomal SmN/B/Bâ€™ proteins by the RBM5 OCRE domain in alternative splicing regulation published pages: , ISSN: 2050-084X, DOI:	elife 5	2019-07-05
2016	Endre SebestyÃ©n, Babita Singh, BelÃ©n MiÃ±ana, AmadÃs PagÃ¨s, Francesca Mateo, Miguel Angel Pujana, Juan ValcÃ¡rcel, Eduardo Eyras Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks published pages: 732-744, ISSN: 1088-9051, DOI: 10.1101/gr.199935.115	Genome Research 26/6	2019-07-05
2016	Panagiotis Papasaikas, Juan ValcÃ¡rcel The Spliceosome: The Ultimate RNA Chaperone and Sculptor published pages: 33-45, ISSN: 0968-0004, DOI: 10.1016/j.tibs.2015.11.003	Trends in Biochemical Sciences 41/1	2019-07-05
2016	Julien, P., MiÃ±ana, B., ValcÃ¡rcel, J. and Lehner, B* * Co-corresponding authors* The complete local genotype-phenotype landscape for the alternative splicing of a human exon published pages: 11558, ISSN: 2041-1723, DOI:	Nature Communications 7	2019-07-05
2017	Luisa Vigevani, AndrÃ© Gohr, Thomas Webb, Manuel Irimia, Juan ValcÃ¡rcel Molecular basis of differential 3â€² splice site sensitivity to anti-tumor drugs targeting U2 snRNP published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-02007-z	Nature Communications 8/1	2019-07-05
2017	Metehan Cifdaloz, Lisa Osterloh, Osvaldo GraÃ±a, Erica Riveiro-Falkenbach, Pilar XimÃ©nez-EmbÃºn, Javier MuÃ±oz, Cristina Tejedo, Tonantzin G. Calvo, Panagiotis Karras, David Olmeda, BelÃ©n MiÃ±ana, Gonzalo GÃ³mez-LÃ³pez, Estela CaÃ±on, Eduardo Eyras, Haihong Guo, Ferdinand Kappes, Pablo L. Ortiz-Romero, Jose L. RodrÃguez-Peralto, Diego MegÃas, Juan ValcÃ¡rcel, MarÃa S. Soengas Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1 published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-02353-y	Nature Communications 8/1	2019-07-05
2016	Makowski, K., Vigevani, L., Albericio, F., ValcÃ¡rcel, J. and Ãlvarez, M: Sudemycin K Co-corresponding authors* A synthetic anti-tumor splicing inhibitor variant with improved activity and versatile chemistry published pages: 163-173, ISSN: 1554-8929, DOI:	ACS Chemical Biology 12/1	2019-07-05
2015	Jordi HernÃ¡ndez, Elias Bechara, Doerte Schlesinger, Javier Delgado, Luis Serrano, Juan ValcÃ¡rcel Tumor suppressor properties of the splicing regulatory factor RBM10 published pages: 466-472, ISSN: 1547-6286, DOI: 10.1080/15476286.2016.1144004	RNA Biology 13/4	2019-07-05
2018	Horiuchi, K., Perez-Cerezales, S., Papasaikas, P., LÃ³pez-Cardona, A.P., Ramos-Ibeas, P., Laguna-Barraza, R., Fonseca Balvis, N., Perocuesta, E., FernÃ¡ndez-GonzÃ¡lez, R., Planells, B., Ross, P.J., AlÃ©n, F., Orio, L., Rodriguez de Fonseca, F., Pintado, B., ValcÃ¡rcel, J. and GutiÃ©rrez-AdÃ¡n, A * Co-corresponding authors Impaired spermatogenesis, muscle and erythrocyte function in U12 intron-splicing defective Zrsr1 mutant mice published pages: 143-155, ISSN: 2211-1247, DOI:	Cell Reports 23/1	2019-07-05

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