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MASCP SIGNED

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

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EC-Contrib. €

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Partnership

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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 ES (BARCELONA) coordinator 2˙159˙574.00

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 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

year authors and title journal last update
List of publications.
2016 Mourao, A., Bonnal, S., Warner, L., Soni, K., Bordonné, R., Valcárcel, J. * and Sattler, M. * * Co-corresponding authors
Structural basis for the recognition of proline-rich motifs in spliceosomal SmN/B/B’ proteins by the RBM5 OCRE domain in alternative splicing regulation
published pages: , ISSN: 2050-084X, DOI:
elife 5 2019-07-05
2016 Endre Sebestyén, Babita Singh, Belén Miñana, Amadís Pagès, Francesca Mateo, Miguel Angel Pujana, Juan Valcárcel, 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 Valcárcel
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., Miñana, B., Valcárcel, 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, André Gohr, Thomas Webb, Manuel Irimia, Juan Valcárcel
Molecular basis of differential 3′ 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 Graña, Erica Riveiro-Falkenbach, Pilar Ximénez-Embún, Javier Muñoz, Cristina Tejedo, Tonantzin G. Calvo, Panagiotis Karras, David Olmeda, Belén Miñana, Gonzalo Gómez-López, Estela Cañon, Eduardo Eyras, Haihong Guo, Ferdinand Kappes, Pablo L. Ortiz-Romero, Jose L. Rodríguez-Peralto, Diego Megías, Juan Valcárcel, María 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., Valcárcel, J.* and Álvarez, 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 Hernández, Elias Bechara, Doerte Schlesinger, Javier Delgado, Luis Serrano, Juan Valcárcel
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., López-Cardona, A.P., Ramos-Ibeas, P., Laguna-Barraza, R., Fonseca Balvis, N., Perocuesta, E., Fernández-González, R., Planells, B., Ross, P.J., Alén, F., Orio, L., Rodriguez de Fonseca, F., Pintado, B., Valcárcel, J*. and Gutiérrez-Adán, 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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