Our laboratory is interested in how primary transcripts of protein-coding genes (pre-mRNAs) are processed in different ways to generate multiple mRNAs encoding different proteins which often have distinct, even antagonistic functions. One example of this, which we study in the lab, is shown in Figure 1. A region of Fas pre-mRNA (exon 6) can be included in the mature mRNA after removal of adjacent sequences (introns) by the process known as RNA splicing. Exon 6-containing mRNAs encode the membrane-bound form of the Fas receptor, which upon binding of its ligand (FasL), triggers a cascade of intracellular events that lead to cell death (apoptosis). If exon 6 sequences are excluded from the mature mRNA, however, the encoded protein product is a soluble form of the receptor that prevents apoptosis by squelching the Fas ligand in the extracellular space. Thus, the decision between including or skipping exon 6 can make the difference between life and death for the cell.

The majority of human genes use this process, known as alternative splicing, to regulate gene expression and generate multiple proteins and functional readouts. Furthermore, alterations in splicing underly a growing number of genetic diseases and contribute to a variety of pathologies, including inflammation and cancer.

Our group participates in the activities of the EU-funded European Alternative Splicing Network of Excellence (EURASNET): www.eurasnet.org

Additional information about alternative splicing, projects and publications of the lab can be found in the following web site: http://www.icrea.es/ca/investigadors/index.html

The work of our group focuses on three main topics:

1. How are splice sites recognized in the transcriptome ?
2. How are splice sites regulated ?
3. How does the cell program alternative splicing decisions ?