Extracellular cues: how to alter splicing patterns

MATÍAS BLAUSTEIN; FEDERICO PELISCH; ALBERTO R. KORNBLIHTT; ANABELLA SREBROW

New Hampshire, Estados Unidos

Conferencia; Gordon Research Conference: “The Biology of Post-Trancriptional Gene Regulation"; 2004

Alternative splicing, which generates distinct proteins from a single gene, is considered the main source of proteome variety and about fifty percent of the human genes undergo this process. Fibronectin (FN), the best characterized extracellular matrix glycoprotein, plays a key role in cell adhesive and migratory behavior and contains three alternatively spliced regions providing a relevant model of alternative splicing. In the present work we studied the effect of extracellular signals on the regulation of fibronectin pre-mRNA alternative splicing. To unravel the complex network of signaling pathways that lead to splicing regulation we tested the effect of growth factors as well as soluble factors present in a mesenchymal cell-conditioned medium on alternative splicing. We analyzed the role of cis- and trans- acting factors. Here, we discuss the relevance of diferent signalling kinases, SR protein kinases and SR proteins in transducing the information from the extracellular milieu. We provide evidence for a transduction pathway involving Ras, PI3K, AKT/PKB and the SR protein 9G8. Taken together, these results strengthen our understanding of how extracellular stimuli are converted into changes in splicing patterns.