Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4

Data de publicació electrònica: 07-08-2025

Detalles Bibliográficos
Autores: Bonnal, Sophie, Bajew, Simon, 1994-, Martínez Corral, Rosa, 1991-, Irimia Martínez, Manuel
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/71292
Acceso en línea:http://hdl.handle.net/10230/71292
http://dx.doi.org/10.1038/s41594-025-01634-1
Access Level:acceso embargado
Palabra clave:Microexon
Core spliceosome
Massively Parallel Splicing assays
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spelling Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4Bonnal, SophieBajew, Simon, 1994-Martínez Corral, Rosa, 1991-Irimia Martínez, ManuelMicroexonCore spliceosomeMassively Parallel Splicing assaysData de publicació electrònica: 07-08-2025Microexons are essential for the proper operation of neurons and pancreatic endocrine cells, in which their inclusion depends on the splicing factors SRRM3 and SRRM4 (SRRM3/4). However, in pancreatic cells, lower expression of these regulators limits inclusion to only the most sensitive subset among all neuronal microexons. Although various cis-acting elements can contribute to microexon regulation, how they determine this differential dose response and the corresponding high or low sensitivity to SRRM3/4 remains unknown. Here we use massively parallel splicing assays probing 28,535 variants to show that sensitivity to SRRM4 is conserved across vertebrates. Our data support a regulatory model whereby high or low microexon sensitivity is largely determined by the interplay between core splicing architecture and length constraints. This conclusion is further supported by distinct spliceosome activities in the absence of SRRM3/4 and by a mathematical model that assumes that the two types of microexons differ only in their efficiency to recruit early spliceosomal components.The research was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program (ERC-CoG, grant agreement 101002275 to M.I.) and Spanish Ministry of Science and Innovation (PID2020-115040GB-I00/AEI/10.13039/501100011033 to M.I.). R.M.-C. acknowledges support from RYC2021-033860-I funded by MCIN/AEI/10.13039/501100011033 and by European Union NextGeneration EU/PRTR. CRG acknowledges support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033) and the Generalitat de Catalunya through the CERCA program.Nature Research20252025infoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/71292http://dx.doi.org/10.1038/s41594-025-01634-1reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNat Struct Mol Biol. 2025 Aug 7info:eu-repo/grantAgreement/EC/H2020/101002275info:eu-repo/grantAgreement/ES/2PE/PID2020-115040GB-I00© Springer Nature Publishing AG [Bonnal S, Bajew S, Martinez-Corral R, Irimia M. Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4. Nat Struct Mol Biol. 2025 Aug 7. DOI: 10.1038/s41594-025-01634-1] [http://dx.doi.org/10.1038/s41594-025-01634-1]info:eu-repo/semantics/embargoedAccessoai:recercat.cat:10230/712922026-05-29T05:05:01Z
dc.title.none.fl_str_mv Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
title Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
spellingShingle Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
Bonnal, Sophie
Microexon
Core spliceosome
Massively Parallel Splicing assays
title_short Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
title_full Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
title_fullStr Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
title_full_unstemmed Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
title_sort Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4
dc.creator.none.fl_str_mv Bonnal, Sophie
Bajew, Simon, 1994-
Martínez Corral, Rosa, 1991-
Irimia Martínez, Manuel
author Bonnal, Sophie
author_facet Bonnal, Sophie
Bajew, Simon, 1994-
Martínez Corral, Rosa, 1991-
Irimia Martínez, Manuel
author_role author
author2 Bajew, Simon, 1994-
Martínez Corral, Rosa, 1991-
Irimia Martínez, Manuel
author2_role author
author
author
dc.subject.none.fl_str_mv Microexon
Core spliceosome
Massively Parallel Splicing assays
topic Microexon
Core spliceosome
Massively Parallel Splicing assays
description Data de publicació electrònica: 07-08-2025
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
info
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/71292
http://dx.doi.org/10.1038/s41594-025-01634-1
url http://hdl.handle.net/10230/71292
http://dx.doi.org/10.1038/s41594-025-01634-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Struct Mol Biol. 2025 Aug 7
info:eu-repo/grantAgreement/EC/H2020/101002275
info:eu-repo/grantAgreement/ES/2PE/PID2020-115040GB-I00
dc.rights.none.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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