Cell paper from Alberto Kornblihtt's group

Muñoz, M. J., Pérez Santangelo, S., Paronetto, M. P., de la Mata, M., Pelisch, F., Boireau, S., Glover-Cutter K., Ben-Dov, C., Blaustein, M., Lozano, J. J., Bird, G., Bentley, D., Bertrand, E. & Kornblihtt, A. R. DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell 137, 708-720 (2009). Commented as Leading Edge in Cell 137, 600-602 (2009).

The Cell paper describes the mechanism by which DNA damage caused by UV irradiation triggers a cell response that affects alternative splicing of many genes, including the upregulation of pro-apoptotic splicing isoforms of Bcl-x and caspase 9. Promotion of apoptosis through this mechanism is relevant to prevent the eventual spreading of UV-induced, unrepaired mutations. In other words, it's better to die than to spread the mutation. The key feature of this mechanism is that, through DNA damage, UV light promotes the hyperphosphorylation of the carboxy terminal domain of RNA Polymerase II causing a significant reduction in transcription elongation, which in turn affects co-transcriptional alternative splicing decisions.