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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Detalhes bibliográficos
Autor: Bajew, Simon
Tipo de documento: tese
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:CBUC, CESCA
Repositório:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/674111
Acesso em linha:http://hdl.handle.net/10803/674111
Access Level:Acceso aberto
Palavra-chave: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
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spelling SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine functionBajew, SimonAlternative splicingMicroexonsEndocrine pancreasCis-regulatory elementsHigh-throughput libraryEmpalme alternativoMicroexonesPancreas endocrinoElementos reguladores en cisLibrería de alto rendimiento616.4Alternative 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.El empalme alternativo es un proceso postranscripcional que permite la generación de múltiples isoformas de transcripción y proteína a partir de un solo gen mediante el procesamiento diferencial de exones e intrones. Esta tesis se centra en los microexones, la clase más corta de exones, previamente caracterizados en el sistema nervioso de los vertebrados como funcionalmente importantes y regulados por la proteína SRRM4. Aquí, proporcionamos evidencias para un programa de regulación de microexones en el páncreas endocrino que está controlado por SRRM3, un parálogo de SRRM4 que comparte un dominio ancestral requerido para la inclusión de microexones. Encontramos que el páncreas endocrino utiliza un subconjunto del programa de microexones neurales, formando un programa anidado de microexones neuroendocrinos. También mostramos que la correcta inclusión de estos microexones (EndoMICs) es importante para la función secretora de los islotes pancreáticos. Finalmente, proporcionamos información sobre los mecanismos por los cuales el programa anidado de microexones neuroendocrinos se regula de manera diferencial entre los tejidos neurales y pancreáticos endocrinosPrograma de doctorat en BiomedicinaValcárcel, J. (Juan)Irimia, ManuelUniversitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut202220242022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion184 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/674111TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc/4.0/http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6741112026-06-14T12:46:07Z
dc.title.none.fl_str_mv SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
title SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
spellingShingle SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
Bajew, Simon
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
title_short SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
title_full SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
title_fullStr SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
title_full_unstemmed SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
title_sort SRRM3 regulates a subprogram of highly sensitive microexons important for pancreatic endocrine function
dc.creator.none.fl_str_mv Bajew, Simon
author Bajew, Simon
author_facet Bajew, Simon
author_role author
dc.contributor.none.fl_str_mv Valcárcel, J. (Juan)
Irimia, Manuel
Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
dc.subject.none.fl_str_mv 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
topic 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
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/674111
url http://hdl.handle.net/10803/674111
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 184 p.
application/pdf
application/pdf
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423204386209793
score 15,300719

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