MASCP SIGNED
Mechanisms of alternative pre-mRNA splicing regulation in cancer and pluripotent cells
Total Cost €
0EC-Contrib. €
0Partnership
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Project "MASCP" data sheet
The following table provides information about the project.
| Coordinator |
FUNDACIO CENTRE DE REGULACIO GENOMICA
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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, AmadÃs 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. RodrÃguez-Peralto, Diego MegÃas, Juan Valcárcel, 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., Valcárcel, 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 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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