Cel "Alternative pre-mRNA splicing is more a rule than an exception because it is estimated to affect the expression of nearly 65%of human genes. The importance of alternative splicing (AS) is confirmed by findings that mutations that affect it are frequent in human hereditary disease and because AS factors can be misregulated in cancer. It is now well established that splicing can be cotranscriptional and that AS regulation not only depends on the interaction of splicing factors with their target sequences in the pre-mRNA, but is also coupled to RNA polymerase II (Pol II) transcription, similar to what happens with other pre-mRNA processing reactions. A unique feature of this polymerase is the presence of a highly repetitive carboxy terminal domain (CTD), which is subject to multiple regulatory post-translational modifications. The ways in which transcription, and more precisely CTD phosphorylation events, regulate AS involve both the association of splicing factors to the transcribing polymerase (recruitment coupling) and modulation of Pol II elongation rates (kinetic coupling). Moreover, it has been recently shown that chromatin template modifications, through Pol II elongation inhibition, can influence AS. But the mechanisms involved in alternative splicing regulation, especially those acting through coupling with transcription, have not been deeply studied in in vivo models. Much of our knowledge comes from in vitro approaches, where conditions can be precisely controlled at the expense of losing several levels of regulation present in intact cells. In this project, we plan to address two major questions: 1) how hyperphosphorylation of Pol II induces a decrease in Pol II elongation rate and 2) how AS changes caused through modifications in Pol II activity and chromatin structure are regulated during the cell cycle. To tackle these questions, we will take advantage of recent findings obtained by both the Kornblihtt and the Valcárcel labs." Dziedzina nauki natural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsRNA Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2010-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development" Zaproszenie do składania wniosków FP7-PEOPLE-2010-IOF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IOF - International Outgoing Fellowships (IOF) Koordynator FUNDACIO CENTRE DE REGULACIO GENOMICA Wkład UE € 191 284,00 Adres CARRER DOCTOR AIGUADER 88 08003 Barcelona Hiszpania Zobacz na mapie Region Este Cataluña Barcelona Rodzaj działalności Research Organisations Kontakt administracyjny Mariana Morlans (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
