Translational activity of the splicing factor SRSF1 is required for development and cilia function

Autores
Haward, Fiona; Maslon, Magdalena; Yeyati, Patricia; Bellora, Nicolás; Hansen, Jan; Aitken, Stuart; Lawson, Jennifer; von Kriegsheim, Alex; Wachten, Dagmar; Mill, Pleasantine; Adams, Ian; Caceres, Javier
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. SR proteins regulate pre-mRNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in Srsf1 to create a mouse model harboring an SRSF1 protein that is retained exclusively in the nucleus. Srsf1NRS/NRS mutants displayed small body size, hydrocephalus and immotile sperm, all traits associated with ciliary defects. We observed reduced translation of a subset of mRNAs and decreased abundance of proteins involved in multiciliogenesis, with disruption of ciliary ultrastructure and motility. These results highlight the physiological requirement of splicing factor shuttling to reprogram gene expression networks at the level of mRNA translation in the context of high cellular demand for cilia function.
Fil: Haward, Fiona. University of Edinburgh; Reino Unido
Fil: Maslon, Magdalena. University of Edinburgh; Reino Unido
Fil: Yeyati, Patricia. University of Edinburgh; Reino Unido
Fil: Bellora, Nicolás. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Instituto de Tecnologias Nucleares Para la Salud.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hansen, Jan. Universitat Bonn; Alemania
Fil: Aitken, Stuart. University of Edinburgh; Reino Unido
Fil: Lawson, Jennifer. University of Edinburgh; Reino Unido
Fil: von Kriegsheim, Alex. University of Edinburgh; Reino Unido
Fil: Wachten, Dagmar. Universitat Bonn; Alemania
Fil: Mill, Pleasantine. University of Edinburgh; Reino Unido
Fil: Adams, Ian. University of Edinburgh; Reino Unido
Fil: Caceres, Javier. University of Edinburgh; Reino Unido
Materia
COMPUTATIONAL GENOMICS
SR PROTEINS
SRSF1
ALTERNATIVE SPLICING
MRNA TRANSLATION
CILIA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/183650
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/183650
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Translational activity of the splicing factor SRSF1 is required for development and cilia functionHaward, FionaMaslon, MagdalenaYeyati, PatriciaBellora, NicolásHansen, JanAitken, StuartLawson, Jennifervon Kriegsheim, AlexWachten, DagmarMill, PleasantineAdams, IanCaceres, JavierCOMPUTATIONAL GENOMICSSR PROTEINSSRSF1ALTERNATIVE SPLICINGMRNA TRANSLATIONCILIAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. SR proteins regulate pre-mRNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in Srsf1 to create a mouse model harboring an SRSF1 protein that is retained exclusively in the nucleus. Srsf1NRS/NRS mutants displayed small body size, hydrocephalus and immotile sperm, all traits associated with ciliary defects. We observed reduced translation of a subset of mRNAs and decreased abundance of proteins involved in multiciliogenesis, with disruption of ciliary ultrastructure and motility. These results highlight the physiological requirement of splicing factor shuttling to reprogram gene expression networks at the level of mRNA translation in the context of high cellular demand for cilia function.Fil: Haward, Fiona. University of Edinburgh; Reino UnidoFil: Maslon, Magdalena. University of Edinburgh; Reino UnidoFil: Yeyati, Patricia. University of Edinburgh; Reino UnidoFil: Bellora, Nicolás. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Instituto de Tecnologias Nucleares Para la Salud.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hansen, Jan. Universitat Bonn; AlemaniaFil: Aitken, Stuart. University of Edinburgh; Reino UnidoFil: Lawson, Jennifer. University of Edinburgh; Reino UnidoFil: von Kriegsheim, Alex. University of Edinburgh; Reino UnidoFil: Wachten, Dagmar. Universitat Bonn; AlemaniaFil: Mill, Pleasantine. University of Edinburgh; Reino UnidoFil: Adams, Ian. University of Edinburgh; Reino UnidoFil: Caceres, Javier. University of Edinburgh; Reino UnidoCold Spring Harbor Labs Press2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/183650Haward, Fiona; Maslon, Magdalena; Yeyati, Patricia; Bellora, Nicolás; Hansen, Jan; et al.; Translational activity of the splicing factor SRSF1 is required for development and cilia function; Cold Spring Harbor Labs Press; bioRxiv; 2020; 11-2020; 1-632692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2020.09.04.263251v2info:eu-repo/semantics/altIdentifier/doi/10.1101/2020.09.04.263251info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:19:13Zoai:ri.conicet.gov.ar:11336/183650instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:19:14.193CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Translational activity of the splicing factor SRSF1 is required for development and cilia function
title Translational activity of the splicing factor SRSF1 is required for development and cilia function
spellingShingle Translational activity of the splicing factor SRSF1 is required for development and cilia function
Haward, Fiona
COMPUTATIONAL GENOMICS
SR PROTEINS
SRSF1
ALTERNATIVE SPLICING
MRNA TRANSLATION
CILIA
title_short Translational activity of the splicing factor SRSF1 is required for development and cilia function
title_full Translational activity of the splicing factor SRSF1 is required for development and cilia function
title_fullStr Translational activity of the splicing factor SRSF1 is required for development and cilia function
title_full_unstemmed Translational activity of the splicing factor SRSF1 is required for development and cilia function
title_sort Translational activity of the splicing factor SRSF1 is required for development and cilia function
dc.creator.none.fl_str_mv Haward, Fiona
Maslon, Magdalena
Yeyati, Patricia
Bellora, Nicolás
Hansen, Jan
Aitken, Stuart
Lawson, Jennifer
von Kriegsheim, Alex
Wachten, Dagmar
Mill, Pleasantine
Adams, Ian
Caceres, Javier
author Haward, Fiona
author_facet Haward, Fiona
Maslon, Magdalena
Yeyati, Patricia
Bellora, Nicolás
Hansen, Jan
Aitken, Stuart
Lawson, Jennifer
von Kriegsheim, Alex
Wachten, Dagmar
Mill, Pleasantine
Adams, Ian
Caceres, Javier
author_role author
author2 Maslon, Magdalena
Yeyati, Patricia
Bellora, Nicolás
Hansen, Jan
Aitken, Stuart
Lawson, Jennifer
von Kriegsheim, Alex
Wachten, Dagmar
Mill, Pleasantine
Adams, Ian
Caceres, Javier
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COMPUTATIONAL GENOMICS
SR PROTEINS
SRSF1
ALTERNATIVE SPLICING
MRNA TRANSLATION
CILIA
topic COMPUTATIONAL GENOMICS
SR PROTEINS
SRSF1
ALTERNATIVE SPLICING
MRNA TRANSLATION
CILIA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. SR proteins regulate pre-mRNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in Srsf1 to create a mouse model harboring an SRSF1 protein that is retained exclusively in the nucleus. Srsf1NRS/NRS mutants displayed small body size, hydrocephalus and immotile sperm, all traits associated with ciliary defects. We observed reduced translation of a subset of mRNAs and decreased abundance of proteins involved in multiciliogenesis, with disruption of ciliary ultrastructure and motility. These results highlight the physiological requirement of splicing factor shuttling to reprogram gene expression networks at the level of mRNA translation in the context of high cellular demand for cilia function.
Fil: Haward, Fiona. University of Edinburgh; Reino Unido
Fil: Maslon, Magdalena. University of Edinburgh; Reino Unido
Fil: Yeyati, Patricia. University of Edinburgh; Reino Unido
Fil: Bellora, Nicolás. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Instituto de Tecnologias Nucleares Para la Salud.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hansen, Jan. Universitat Bonn; Alemania
Fil: Aitken, Stuart. University of Edinburgh; Reino Unido
Fil: Lawson, Jennifer. University of Edinburgh; Reino Unido
Fil: von Kriegsheim, Alex. University of Edinburgh; Reino Unido
Fil: Wachten, Dagmar. Universitat Bonn; Alemania
Fil: Mill, Pleasantine. University of Edinburgh; Reino Unido
Fil: Adams, Ian. University of Edinburgh; Reino Unido
Fil: Caceres, Javier. University of Edinburgh; Reino Unido
description Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. SR proteins regulate pre-mRNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in Srsf1 to create a mouse model harboring an SRSF1 protein that is retained exclusively in the nucleus. Srsf1NRS/NRS mutants displayed small body size, hydrocephalus and immotile sperm, all traits associated with ciliary defects. We observed reduced translation of a subset of mRNAs and decreased abundance of proteins involved in multiciliogenesis, with disruption of ciliary ultrastructure and motility. These results highlight the physiological requirement of splicing factor shuttling to reprogram gene expression networks at the level of mRNA translation in the context of high cellular demand for cilia function.
publishDate 2020
dc.date.none.fl_str_mv 2020-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/183650
Haward, Fiona; Maslon, Magdalena; Yeyati, Patricia; Bellora, Nicolás; Hansen, Jan; et al.; Translational activity of the splicing factor SRSF1 is required for development and cilia function; Cold Spring Harbor Labs Press; bioRxiv; 2020; 11-2020; 1-63
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/183650
identifier_str_mv Haward, Fiona; Maslon, Magdalena; Yeyati, Patricia; Bellora, Nicolás; Hansen, Jan; et al.; Translational activity of the splicing factor SRSF1 is required for development and cilia function; Cold Spring Harbor Labs Press; bioRxiv; 2020; 11-2020; 1-63
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2020.09.04.263251v2
info:eu-repo/semantics/altIdentifier/doi/10.1101/2020.09.04.263251
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Labs Press
publisher.none.fl_str_mv Cold Spring Harbor Labs Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842981047017406464
score 12.48226

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