SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function

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 sy...

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Detalles Bibliográficos
Autor: Bajew, Simon
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/674111
Acceso en línea:http://hdl.handle.net/10803/674111
Access Level:acceso abierto
Palabra clave:Alternative splicing
Microexons
Endocrine pancreas
Cis-regulatory elements
High-throughput library
Empalme alternativo
Microexones
Pancreas endocrino
Elementos reguladores en cis
Librería de alto rendimiento
616.4
Descripción
Sumario: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.