Splicing regulator SLU7 is essential for maintaining liver homeostasis

Elizalde-Arbilla, M. (María)|||/items/0e4303b3-5b3e-4a7f-acc3-e0d5f1f51089; Urtasun, R. (Raquel)|||/items/d142c944-e4b4-46d5-9d1a-074bddcc733c; Azkona, M.T. (María Teresa)|||/items/e5b12333-46f8-4755-a9ef-245a7d3d0bf5; Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356; Goñi, S. (Saioa)|||/items/30c9118a-59e0-41e1-9d9a-a41414437869; García-Irigoyen, O. (Oihane)|||/items/c66c75d2-9ffd-4e47-a691-7907b76cea2f; Uriarte-Díaz-Varela, I. (Iker)|||/items/607bacbb-b72c-46cd-89fb-455b9f6ddb27; Segura, V. (Víctor)|||/items/a2676e21-45bc-4e5e-958f-bdfa042e02d4; Collantes, M. (María)|||/items/102ad3e7-3f57-4958-8e97-39af1c92626b; Scala, M. (Marianna) Di|||/items/d637d8a4-cab9-48f9-8345-34c46046cb39; Lujambio, A. (Amaya)|||/items/30897a02-ab11-452c-bfb3-5017a80b4b07; Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71; Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f; Berasain-Lasarte, C. (Carmen)|||/items/f1d61c19-1753-4442-a3fd-cc90220e84a0

Splicing regulator SLU7 is essential for maintaining liver homeostasis

A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential....

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Detalles Bibliográficos
Autores:	Elizalde-Arbilla, M. (María)\|\|\|/items/0e4303b3-5b3e-4a7f-acc3-e0d5f1f51089, Urtasun, R. (Raquel)\|\|\|/items/d142c944-e4b4-46d5-9d1a-074bddcc733c, Azkona, M.T. (María Teresa)\|\|\|/items/e5b12333-46f8-4755-a9ef-245a7d3d0bf5, Latasa, M.U. (María Ujué)\|\|\|/items/e1e74596-1598-4722-a96a-7bdd7cdec356, Goñi, S. (Saioa)\|\|\|/items/30c9118a-59e0-41e1-9d9a-a41414437869, García-Irigoyen, O. (Oihane)\|\|\|/items/c66c75d2-9ffd-4e47-a691-7907b76cea2f, Uriarte-Díaz-Varela, I. (Iker)\|\|\|/items/607bacbb-b72c-46cd-89fb-455b9f6ddb27, Segura, V. (Víctor)\|\|\|/items/a2676e21-45bc-4e5e-958f-bdfa042e02d4, Collantes, M. (María)\|\|\|/items/102ad3e7-3f57-4958-8e97-39af1c92626b, Scala, M. (Marianna) Di\|\|\|/items/d637d8a4-cab9-48f9-8345-34c46046cb39, Lujambio, A. (Amaya)\|\|\|/items/30897a02-ab11-452c-bfb3-5017a80b4b07, Prieto, J. (Jesús)\|\|\|/items/0d9c3dec-4a09-400d-8c83-23ece1096c71, Avila, M.A. (Matías Antonio)\|\|\|/items/3ad9abbb-c18d-445b-86cf-cb76be15419f, Berasain-Lasarte, C. (Carmen)\|\|\|/items/f1d61c19-1753-4442-a3fd-cc90220e84a0
Tipo de recurso:	artículo
Fecha de publicación:	2014
País:	España
Institución:	Universidad de Navarra
Repositorio:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:	inglés
OAI Identifier:	oai:dadun.unav.edu:10171/36167
Acceso en línea:	https://hdl.handle.net/10171/36167
Access Level:	acceso abierto

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spelling	Splicing regulator SLU7 is essential for maintaining liver homeostasisElizalde-Arbilla, M. (María)\|\|\|/items/0e4303b3-5b3e-4a7f-acc3-e0d5f1f51089Urtasun, R. (Raquel)\|\|\|/items/d142c944-e4b4-46d5-9d1a-074bddcc733cAzkona, M.T. (María Teresa)\|\|\|/items/e5b12333-46f8-4755-a9ef-245a7d3d0bf5Latasa, M.U. (María Ujué)\|\|\|/items/e1e74596-1598-4722-a96a-7bdd7cdec356Goñi, S. (Saioa)\|\|\|/items/30c9118a-59e0-41e1-9d9a-a41414437869García-Irigoyen, O. (Oihane)\|\|\|/items/c66c75d2-9ffd-4e47-a691-7907b76cea2fUriarte-Díaz-Varela, I. (Iker)\|\|\|/items/607bacbb-b72c-46cd-89fb-455b9f6ddb27Segura, V. (Víctor)\|\|\|/items/a2676e21-45bc-4e5e-958f-bdfa042e02d4Collantes, M. (María)\|\|\|/items/102ad3e7-3f57-4958-8e97-39af1c92626bScala, M. (Marianna) Di\|\|\|/items/d637d8a4-cab9-48f9-8345-34c46046cb39Lujambio, A. (Amaya)\|\|\|/items/30897a02-ab11-452c-bfb3-5017a80b4b07Prieto, J. (Jesús)\|\|\|/items/0d9c3dec-4a09-400d-8c83-23ece1096c71Avila, M.A. (Matías Antonio)\|\|\|/items/3ad9abbb-c18d-445b-86cf-cb76be15419fBerasain-Lasarte, C. (Carmen)\|\|\|/items/f1d61c19-1753-4442-a3fd-cc90220e84a0A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4α (Hnf4α), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.Dadun. Depósito Académico Digital Universidad de Navarra20142014-07-1520142014-01-0120142014-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/36167reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/361672026-06-21T12:47:57Z
dc.title.none.fl_str_mv	Splicing regulator SLU7 is essential for maintaining liver homeostasis
title	Splicing regulator SLU7 is essential for maintaining liver homeostasis
spellingShingle	Splicing regulator SLU7 is essential for maintaining liver homeostasis Elizalde-Arbilla, M. (María)\|\|\|/items/0e4303b3-5b3e-4a7f-acc3-e0d5f1f51089
title_short	Splicing regulator SLU7 is essential for maintaining liver homeostasis
title_full	Splicing regulator SLU7 is essential for maintaining liver homeostasis
title_fullStr	Splicing regulator SLU7 is essential for maintaining liver homeostasis
title_full_unstemmed	Splicing regulator SLU7 is essential for maintaining liver homeostasis
title_sort	Splicing regulator SLU7 is essential for maintaining liver homeostasis
dc.creator.none.fl_str_mv	Elizalde-Arbilla, M. (María)\|\|\|/items/0e4303b3-5b3e-4a7f-acc3-e0d5f1f51089 Urtasun, R. (Raquel)\|\|\|/items/d142c944-e4b4-46d5-9d1a-074bddcc733c Azkona, M.T. (María Teresa)\|\|\|/items/e5b12333-46f8-4755-a9ef-245a7d3d0bf5 Latasa, M.U. (María Ujué)\|\|\|/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Goñi, S. (Saioa)\|\|\|/items/30c9118a-59e0-41e1-9d9a-a41414437869 García-Irigoyen, O. (Oihane)\|\|\|/items/c66c75d2-9ffd-4e47-a691-7907b76cea2f Uriarte-Díaz-Varela, I. (Iker)\|\|\|/items/607bacbb-b72c-46cd-89fb-455b9f6ddb27 Segura, V. (Víctor)\|\|\|/items/a2676e21-45bc-4e5e-958f-bdfa042e02d4 Collantes, M. (María)\|\|\|/items/102ad3e7-3f57-4958-8e97-39af1c92626b Scala, M. (Marianna) Di\|\|\|/items/d637d8a4-cab9-48f9-8345-34c46046cb39 Lujambio, A. (Amaya)\|\|\|/items/30897a02-ab11-452c-bfb3-5017a80b4b07 Prieto, J. (Jesús)\|\|\|/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Avila, M.A. (Matías Antonio)\|\|\|/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Berasain-Lasarte, C. (Carmen)\|\|\|/items/f1d61c19-1753-4442-a3fd-cc90220e84a0
author	Elizalde-Arbilla, M. (María)\|\|\|/items/0e4303b3-5b3e-4a7f-acc3-e0d5f1f51089
author_facet	Elizalde-Arbilla, M. (María)\|\|\|/items/0e4303b3-5b3e-4a7f-acc3-e0d5f1f51089 Urtasun, R. (Raquel)\|\|\|/items/d142c944-e4b4-46d5-9d1a-074bddcc733c Azkona, M.T. (María Teresa)\|\|\|/items/e5b12333-46f8-4755-a9ef-245a7d3d0bf5 Latasa, M.U. (María Ujué)\|\|\|/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Goñi, S. (Saioa)\|\|\|/items/30c9118a-59e0-41e1-9d9a-a41414437869 García-Irigoyen, O. (Oihane)\|\|\|/items/c66c75d2-9ffd-4e47-a691-7907b76cea2f Uriarte-Díaz-Varela, I. (Iker)\|\|\|/items/607bacbb-b72c-46cd-89fb-455b9f6ddb27 Segura, V. (Víctor)\|\|\|/items/a2676e21-45bc-4e5e-958f-bdfa042e02d4 Collantes, M. (María)\|\|\|/items/102ad3e7-3f57-4958-8e97-39af1c92626b Scala, M. (Marianna) Di\|\|\|/items/d637d8a4-cab9-48f9-8345-34c46046cb39 Lujambio, A. (Amaya)\|\|\|/items/30897a02-ab11-452c-bfb3-5017a80b4b07 Prieto, J. (Jesús)\|\|\|/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Avila, M.A. (Matías Antonio)\|\|\|/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Berasain-Lasarte, C. (Carmen)\|\|\|/items/f1d61c19-1753-4442-a3fd-cc90220e84a0
author_role	author
author2	Urtasun, R. (Raquel)\|\|\|/items/d142c944-e4b4-46d5-9d1a-074bddcc733c Azkona, M.T. (María Teresa)\|\|\|/items/e5b12333-46f8-4755-a9ef-245a7d3d0bf5 Latasa, M.U. (María Ujué)\|\|\|/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Goñi, S. (Saioa)\|\|\|/items/30c9118a-59e0-41e1-9d9a-a41414437869 García-Irigoyen, O. (Oihane)\|\|\|/items/c66c75d2-9ffd-4e47-a691-7907b76cea2f Uriarte-Díaz-Varela, I. (Iker)\|\|\|/items/607bacbb-b72c-46cd-89fb-455b9f6ddb27 Segura, V. (Víctor)\|\|\|/items/a2676e21-45bc-4e5e-958f-bdfa042e02d4 Collantes, M. (María)\|\|\|/items/102ad3e7-3f57-4958-8e97-39af1c92626b Scala, M. (Marianna) Di\|\|\|/items/d637d8a4-cab9-48f9-8345-34c46046cb39 Lujambio, A. (Amaya)\|\|\|/items/30897a02-ab11-452c-bfb3-5017a80b4b07 Prieto, J. (Jesús)\|\|\|/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Avila, M.A. (Matías Antonio)\|\|\|/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Berasain-Lasarte, C. (Carmen)\|\|\|/items/f1d61c19-1753-4442-a3fd-cc90220e84a0
author2_role	author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Dadun. Depósito Académico Digital Universidad de Navarra
description	A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4α (Hnf4α), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.
publishDate	2014
dc.date.none.fl_str_mv	2014 2014-07-15 2014 2014-01-01 2014 2014-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10171/36167
url	https://hdl.handle.net/10171/36167
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra
instname_str	Universidad de Navarra
reponame_str	Dadun. Depósito Académico Digital de la Universidad de Navarra
collection	Dadun. Depósito Académico Digital de la Universidad de Navarra
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Splicing regulator SLU7 is essential for maintaining liver homeostasis

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