GROUP LEADER:
Manuel Irimia
POSTDOCTORAL FELLOWS:
Bárbara Pernaute, Thomas Spruce, Yamile Marquez, Elisabeth Kita
PhD STUDENTS:
Javier Tapial, Chris Wyatt, Laura López-Blanch, Victoria Rodriguez-Vaello, Antonio Torres-Méndez, Patryk Polinski.
TECHNICIANS:
Jon Permanyer, Marta Miret, André Gohr
Our group is interested in understanding the roles that alternative splicing plays in vertebrate embryonic development, and how novel transcript variants have contributed to shape our unique development and body plan during evolution.
Alternative splicing – the differential processing of introns and exons – is the most widespread contributor to vertebrate transcriptomic diversity, impacting more than 95% of human multiexonic genes. However, the role of alternative splicing in vertebrate development and its contribution to evolution is largely unknown.
To address this question, our lab combines high throughput next-generation sequencing (NGS) analyses with cellular and developmental biology assays in multiple vertebrate and non-vertebrate models, with a particular focus on neural and pluripotent systems. In particular, we are currently focusing on two highly contrasting systems: (i) early mammalian embryogenesis and (ii) vertebrate central nervous system (CNS) development. These two developmental contexts show radically distinct characteristics. On the one hand, early embryogenesis captures in vivo pluripotency and the first cell fate decisions, involves relatively simple morphogenetic processes, and shows particularly high evolutionary rates. On the other hand, vertebrate brains are extremely complex systems of highly differentiated cell types that develop through very specialized processes (e.g. neuritogenesis, axon guidance, migration, etc.). Furthermore, neural-specific post-transcriptional events, especially microexons, are exceptionally conserved. Thus, combining both biological systems will provide highly complementary insights into the roles of transcriptomic diversification in development and evolution.
Vigevani L, Gohr A, Webb T, Irimia M, Valcárcel J.
“Molecular basis of differential 3′ splice site sensitivity to anti-tumor drugs targeting U2 snRNP.”
Nat Commun, 8:2100 (2017).
Burguera D, Marquez Y, Racioppi C, Permanyer J, Torres-Méndez A, Esposito R, Albuixech-Crespo B, Fanlo L, D’Agostino Y, Gohr A, Navas-Perez E, Riesgo A, Cuomo C, Benvenuto G, Christiaen LA, Martí E, D’Aniello S, Spagnuolo A, Ristoratore F, Arnone MI#, Garcia-Fernàndez J#, Irimia M#.
“Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes.”
Nat Commun, 8:1799 (2017).
Tapial J, Ha KCH, Sterne-Weiler T, Gohr A, Braunschweig U, Hermoso-Pulido A, Quesnel-Vallières M, Permanyer J, Sodaei R, Marquez Y, Cozzuto L, Wang X, Gómez-Velázquez M, Rayon T, Manzanares M, Ponomarenko J, Blencowe BJ#, Irimia M#.
“An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms.”
Genome Res, 27:1759-68 (2017).
Albuixech-Crespo B, Lopez-Blanch L, Burguera D, Maeso I, Sánchez Arrones L, Moreno-Bravo JA, Somorjai I, Pascual-Anaya J, Puelles E, Bovolenta P, Garcia-Fernàndez J#, Puelles L#, Irimia M#, Ferran JL#.
“Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.”
PLoS Biol, 15: e2001573 (2017).
Muñoz MJ, Moreno NN, Giono LE, Cambindo Botto A, Dujardin G, Bastianello G, Lavore S, Torres-Méndez A, Menck CFM, Blencowe BJ, Irimia M, Foiani M, and Kornblihtt AR.
“Major roles of cyclobutane primidine dimers, nucleotide excision repair and ATR in the alternative splicing response to UV irradiation.”
Cell Reports, 18: 2868–79 (2017).
* Co-first author # Co-corresponding author.
![The functional evolution of an epithelial-associated alternative splicing factor (Esrp) across multiple scales of complexity in deuterostomes was shown to follow an hourglass-like model, in which the functions at the molecular (bottom) and organismal (top) levels are highly flexible, but are much more constrained at the intermediate cellular level. [Burguera et al, Nature Comm 2017]](https://annualreport2017.crg.eu/wp-content/uploads/2018/06/m-irimia-fig-01.jpg "Fig. 1")
![We released VastDB (http://vastdb.crg.eu), the most comprehensive and data-rich database of alternative splicing events published so far. In addition to filling a major need in the field of alternative splicing, the analysis of these datasets uncovered a novel regulatory type of AS events (termed PanAS), which are alternatively spliced in virtually all cell and tissue types, even at the single cell level. These events, which are enriched in DNA binding proteins and transcriptional regulators, provide an orthogonal functional layer to the most widely studied tissue-specific AS events. [Tapial et al, Genome Res 2017]](https://annualreport2017.crg.eu/wp-content/uploads/2018/06/m-irimia-fig-02-600x400.jpg "Fig. 2")
