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Josep Vilardell: Molecular mechanisms of pre-mRNA splicing

Lab Presentation

Our research is focused on the molecular mechanisms of the regulation of pre-mRNA splicing, using the budding yeast Saccharomyces cerevisiae and human cells as working systems.

Research Lines

These are our general aims:

We are working to uncover new strategies of splicing regulation by following variations in cellular splicing in several cell types and under different conditions.
We have started by deciphering the spliceosomal code to select intronic 3' ends (3' splice site or 3'ss). Our data revealed that in a significant number of introns the pre-mRNA itself is capable to alter 3'ss selection by adopting different conformations. How these changes can be mediated by splicing factors is still unknown, and to address this we have isolated mutants in splicing factors that display alterations in the spliceosomal code for 3' ss selection. We are also determining whether mutations linked to disease have a role in this code.
We are studying how changes in splicing contribute to the altered ribosomal function observed in cancer cells.
It is known that the nucleolus, where the cell makes ribosomes, is altered in tumor cells; and that unbalances in ribosomal protein production lead to defects in ribosome biosynthesis. Moreover, several ribosomal proteins act as a link between nucleolar stress and the cell cycle control. Interestingly, there are examples documenting how regulated splicing affects ribosomal protein function across evolution, from yeast to man. Thus, we have started analyzing RNASeq data from tumors to discern the contribution to the cancer phenotype from alterations in regulated splicing in transcripts encoding ribosomal proteins
We are dissecting the control of RPL30 splicing by its own product, the ribosomal protein L30.
We know that recognition of the intronic branch site by U2 is repressed in RPL30 upon L30 binding. This system of repression is of particular interest because the data suggest that repression occurs by blocking a conformational change of the spliceosome. This is a strategy for splicing regulation that is still poorly understood. In addition, we investigate what are the effects of changes in chromatin on RPL30 splicing control.
We ask why particular yeast "introns", are not being spliced, or are but poorly (according to Bioinformatics and high throughput data).
The location of these "introns" suggests that the yeast spliceosome is susceptible to "exon definition" strategies, thought to be absent in this organism. Exon definition is however a critical component in human alternative splicing, yet it is not fully understood. Thus, having a model system to address particular aspects of this process will be productive.
Josep Vilardell Trench
  • Josep Vilardell
  • C/ Baldiri Reixac, 10-12
  • 08028 Barcelona, Spain
  • Phone: +34 93 4020549 / +34 93 4020532
  • E-mail:

Principal Investigator

Past students

  • Ribosomal proteins as novel players in tumorigenesis. Antonio de Las Heras-Rubio, Laura Perucho, Rosanna Paciucci, Josep Vilardell, and Matilde Lleonart. Cancer and Metastasis Reviews [Epub ahead of print] (2013) Abstract
  • Intronic features that determine the selection of the 3' splice site. Jorge Pérez-Valle and Josep Vilardell. Wiley Interdiscip Rev RNA. Sep-Oct;3(5): 707-717 (2012) Abstract
  • RNA secondary structure mediates alternative 3'ss selection in Saccharomyces cerevisiae. Mireya Plass, Carles Codony-Servat, Pedro Gabriel Ferreira, Josep Vilardell, and Eduardo Eyras. RNA Jun;18(6):1103-15 (2012) Abstract
  • Regulated pre-mRNA Splicing: The Ghostwriter of the Eukaryotic Genome. Tracy L. Johnson and Josep Vilardell. Biochim. Biophys. Acta 1819: 538–545 (2012) Abstract
  • Deciphering 3'ss selection in the yeast genome reveals an RNA thermosensor that mediates alternative splicing. Markus Meyer, Mireya Plass*, Jorge Pérez-Valle*, Eduardo Eyras, and Josep Vilardell. (*Equal contribution). Molecular Cell 43: 1033-1039 (2011) Abstract, (Science Editor's Choice 30 Sept)
  • SUS1 introns are required for efficient mRNA nuclear export in yeast. Bernardo Cuenca-Bono&, Varinia García-Molinero&, Pau Pascual-García, Hernan Dopazo, Ana Llopis1, Josep Vilardell*, and Susana Rodríguez-Navarro*. (&: Equal contribution *: corresponding author). Nucleic Acids Research  Oct 1;39(19): 8599-611 (2011) Abstract
  • RPL30 regulation of splicing reveals distinct roles for Cbp80 in U1 and U2 snRNP cotranscriptional recruitmentMireia Bragulat, Markus Meyer, Sara Macías, Maria Camats, Mireia Labrador, and Josep VilardellRNA Oct;16(10): 2033-2041 (2010) AbstractSupplemental Material
  • The quest for a message: budding yeast, a model organism to study the control of pre-mRNA splicing. Markus Meyer and Josep VilardellBriefings in Functional Genomics & Proteomics 8(1):60-7 (2009)Abstract
  • L30 binds the nascent RPL30 transcript to repress U2 snRNP recruitmentMacías S, Bragulat M, Tardiff DF, Vilardell JMolecular Cell 30(6):732-42  (2008). Abstract
  • Powering a two-stroke RNA engineJuan Valcárcel, Josep VilardellNature Structural & Molecular Biology 14(7):574-6 (2007)PubMed
  • Repositioning of the reaction intermediate within the catalytic center of the spliceosomeKonarska MM, Vilardell J, Query CC. Molecular Cell 21:543-553 (2006). Abstract

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We are currently seeking highly motivated PhD students and postdocs. Candidates are expected to successfully apply to any suitable fellowship (most Spanish fellowships are competitive and selection is based on the candidate's CV).

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