Chromatin and RNA splicing

Alternative splicing is a highly regulated RNA process used by the cell to increase its protein diversity despite a limited coding genome. By generating different mature mRNAs from the same transcribed gene, the cell can easily gain new functions that will impact its phenotype. For instance, changes in alternative splicing are necessary for the sex determination in flies, for light and temperature signaling in plants, and for brain and muscular development in mammals. However, its dysregulation can also lead to disease, as in the case of cancer cells that have taken advantage of alternative splicing to gain new phenotypic traits essential for their adaptation to the new tumor microenvironment and dissemination into metastatic sites (see Figure). Our aim is to understand the mechanisms orchestrating this cancer-specific splicing reprogramming by looking into an unsuspected novel regulatory layer: the chromatin.