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NEURAL AS SIGNED

Functions and evolutionary impact of transcriptomic novelties in the vertebrate brain

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EC-Contrib. €

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Project "NEURAL 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://vastdb.crg.eu/
 Total cost 1˙498˙852 €
 EC max contribution 1˙498˙852 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-04-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO CENTRE DE REGULACIO GENOMICA ES (BARCELONA) coordinator 1˙498˙852.00

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 Project objective

Alternative splicing (AS) is the largest contributor to transcriptomic diversification in metazoans. In particular, mirroring their unparalleled morphological and cellular complexity, vertebrate brains show the highest levels of regulated AS known in nature. However, the functions of most of these alternative transcripts, and the evolutionary impact that the increased transcriptional complexity has had on the evolution of the vertebrate brain are still widely unexplored. In this project, we will investigate the functions and evolutionary impact of neural AS in vertebrates. We will focus on neural-specific alternative exons that are highly conserved across vertebrate groups (suggesting functional importance), but that are not conserved in invertebrates, and are thus vertebrate-specific genomic novelties. We will term these exons Vertebrate- and Neural-specific Alternatively Spliced (VN-AS) exons. Through a combination of bioinformatics, experimental manipulation in models species, and systems-level network analysis, we aim to: (i) Comprehensively identify VN-AS exons, and study their regulation during vertebrate neurogenesis and nervous system development, using RNA-seq and comparative genomics; (ii) Probe the phenotypic impact of VN-AS exons on vertebrate nervous systems, using the CRISPR-Cas technology for genome editing; and (iii) Investigate how VN-AS exons rewire protein-protein interaction networks in vertebrate neurons – an emergent molecular function for AS –, and whether this rewiring underlies novel functions of VN-AS exons in the vertebrate brains. This project will thus deliver fundamental insight into two major unanswered questions: (i) what are the functions of transcriptomic diversification, and (ii) how does transcriptomic diversification impact organismal evolution. Our results will fill a large gap of knowledge in our current understanding of brain evolution and development, providing a complementary angle to traditional gene expression studies.

 Publications

year authors and title journal last update
List of publications.
2018 Juan Pablo Fernandez, Miguel Angel Moreno-Mateos, Andre Gohr, Liyun Miao, Shun Hang Chan, Manuel Irimia, Antonio J. Giraldez
RES complex is associated with intron definition and required for zebrafish early embryogenesis
published pages: e1007473, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1007473
PLOS Genetics 14/7 2020-02-26
2019 Pinar Ustaoglu, Irmgard U Haussmann, Hongzhi Liao, Antonio Torres-Mendez, Roland Arnold, Manuel Irimia, Matthias Soller
Srrm234, but not canonical SR and hnRNP proteins drive inclusion of Dscam exon 9 variable exons
published pages: rna.071316.119, ISSN: 1355-8382, DOI: 10.1261/rna.071316.119
RNA 2020-02-26
2019 Antonio Torres-Méndez, Sophie Bonnal, Yamile Marquez, Jonathan Roth, Marta Iglesias, Jon Permanyer, Isabel Almudí, Dave O’Hanlon, Tanit Guitart, Matthias Soller, Anne-Claude Gingras, Fátima Gebauer, Fabian Rentzsch, Benjamin J. Blencowe, Juan Valcárcel, Manuel Irimia
A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons
published pages: 691-701, ISSN: 2397-334X, DOI: 10.1038/s41559-019-0813-6
Nature Ecology & Evolution 3/4 2020-02-26
2018 Lorea Blazquez, Warren Emmett, Rupert Faraway, Jose Mario Bello Pineda, Simon Bajew, Andre Gohr, Nejc Haberman, Christopher R. Sibley, Robert K. Bradley, Manuel Irimia, Jernej Ule
Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing
published pages: 496-509.e9, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.09.033
Molecular Cell 72/3 2020-02-26
2018 André Gohr, Manuel Irimia
Matt : Unix tools for alternative splicing analysis
published pages: 130-132, ISSN: 1367-4803, DOI: 10.1093/bioinformatics/bty606
Bioinformatics 35/1 2020-02-26
2018 Alberto Parras, Héctor Anta, María Santos-Galindo, Vivek Swarup, Ainara Elorza, José L. Nieto-González, Sara Picó, Ivó H. Hernández, Juan I. Díaz-Hernández, Eulàlia Belloc, Annie Rodolosse, Neelroop N. Parikshak, Olga Peñagarikano, Rafael Fernández-Chacón, Manuel Irimia, Pilar Navarro, Daniel H. Geschwind, Raúl Méndez, José J. Lucas
Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing
published pages: 441-446, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0423-5
Nature 560/7719 2020-02-26
2019 Francesca Angiolini, Elisa Belloni, Marco Giordano, Matteo Campioni, Federico Forneris, Maria Paola Paronetto, Michela Lupia, Chiara Brandas, Davide Pradella, Anna Di Matteo, Costanza Giampietro, Giovanna Jodice, Chiara Luise, Giovanni Bertalot, Stefano Freddi, Matteo Malinverno, Manuel Irimia, Jon D Moulton, James Summerton, Antonella Chiapparino, Carmen Ghilardi, Raffaella Giavazzi, Daniel Nyqvi
A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.44305
eLife 8 2020-02-26
2018 Ferdinand Marlétaz, Panos N. Firbas, Ignacio Maeso, Juan J. Tena, Ozren Bogdanovic, Malcolm Perry, Christopher D. R. Wyatt, Elisa de la Calle-Mustienes, Stephanie Bertrand, Demian Burguera, Rafael D. Acemel, Simon J. van Heeringen, Silvia Naranjo, Carlos Herrera-Ubeda, Ksenia Skvortsova, Sandra Jimenez-Gancedo, Daniel Aldea, Yamile Marquez, Lorena Buono, Iryna Kozmikova, Jon Permanyer, Alexandra
Amphioxus functional genomics and the origins of vertebrate gene regulation
published pages: 64-70, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0734-6
Nature 564/7734 2020-02-26
2016 Mathieu Quesnel-Vallières, Zahra Dargaei, Manuel Irimia, Thomas Gonatopoulos-Pournatzis, Joanna Y. Ip, Mingkun Wu, Timothy Sterne-Weiler, Shinichi Nakagawa, Melanie A. Woodin, Benjamin J. Blencowe, Sabine P. Cordes
Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders
published pages: 1023-1034, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2016.11.033
Molecular Cell 64/6 2020-02-26
2017 Beatriz Albuixech-Crespo, Laura López-Blanch, Demian Burguera, Ignacio Maeso, Luisa Sánchez-Arrones, Juan Antonio Moreno-Bravo, Ildiko Somorjai, Juan Pascual-Anaya, Eduardo Puelles, Paola Bovolenta, Jordi Garcia-Fernàndez, Luis Puelles, Manuel Irimia, José Luis Ferran
Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain
published pages: e2001573, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.2001573
PLOS Biology 15/4 2020-02-26
2017 Demian Burguera, Yamile Marquez, Claudia Racioppi, Jon Permanyer, Antonio Torres-Méndez, Rosaria Esposito, Beatriz Albuixech-Crespo, Lucía Fanlo, Ylenia D’Agostino, Andre Gohr, Enrique Navas-Perez, Ana Riesgo, Claudia Cuomo, Giovanna Benvenuto, Lionel A. Christiaen, Elisa Martí, Salvatore D’Aniello, Antonietta Spagnuolo, Filomena Ristoratore, Maria Ina Arnone, Jordi Garcia-Fernàndez, Manuel Irimia
Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-01961-y
Nature Communications 8/1 2020-02-26
2016 Neelroop N. Parikshak, Vivek Swarup, T. Grant Belgard, Manuel Irimia, Gokul Ramaswami, Michael J. Gandal, Christopher Hartl, Virpi Leppa, Luis de la Torre Ubieta, Jerry Huang, Jennifer K. Lowe, Benjamin J. Blencowe, Steve Horvath, Daniel H. Geschwind
Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism
published pages: 423-427, ISSN: 0028-0836, DOI: 10.1038/nature20612
Nature 540/7633 2020-02-26
2017 Javier Tapial, Kevin C.H. Ha, Timothy Sterne-Weiler, André Gohr, Ulrich Braunschweig, Antonio Hermoso-Pulido, Mathieu Quesnel-Vallières, Jon Permanyer, Reza Sodaei, Yamile Marquez, Luca Cozzuto, Xinchen Wang, Melisa Gómez-Velázquez, Teresa Rayon, Miguel Manzanares, Julia Ponomarenko, Benjamin J. Blencowe, Manuel Irimia
An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms
published pages: 1759-1768, ISSN: 1088-9051, DOI: 10.1101/gr.220962.117
Genome Research 27/10 2020-02-26
2017 Yann Le Petillon, Guillaume Luxardi, Pierluigi Scerbo, Marie Cibois, Anthony Leon, Lucie Subirana, Manuel Irimia, Laurent Kodjabachian, Hector Escriva, Stephanie Bertrand
Nodal–Activin pathway is a conserved neural induction signal in chordates
published pages: 1192-1200, ISSN: 2397-334X, DOI: 10.1038/s41559-017-0226-3
Nature Ecology & Evolution 1/8 2020-02-26

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