SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
- Autores: Szymon Piotr Bajew
- Directores de la Tesis: Juan Valcárcel Juárez (dir. tes.), Manuel Irimia Martínez (codir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2022
- Idioma: inglés
- Tribunal Calificador de la Tesis: Nuno Luis Barbosa Morais (presid.), Julian König (secret.), Claudia Ghigna (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
- Materias:
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- Resumen
Alternative splicing is a post-transcriptional process that allows the generation of multiple transcript and protein isoforms from a single gene by differential processing of exons and introns. This Thesis focuses on microexons, the shortest class of exons, previously characterised in the nervous system of vertebrates as functionally important and regulated by the protein SRRM4. Here, we provide evidence for a program of microexon regulation in endocrine pancreas that is controlled SRRM3, a paralog of SRRM4 sharing an ancestral domain required for microexon inclusion. We find that endocrine pancreas uses a subset of the neural microexon program, forming a nested program of neuroendocrine microexons. We also show that the correct inclusion of these microexons (EndoMICs) is important for the secretory function of pancreatic islets. Finally, we provide insights into the mechanisms by which the nested program of neuroendocrine microexons is differentially regulated between neural and endocrine pancreatic tissues.
