Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused

Autores
Bruzzone, Lucia; Argüelles, Camilla; Sanial, Matthieu; Miled, Samia; Alvisi, Giorgia; Gonçalves Antunes, Marina; Qasrawi, Fairouz; Holmgren, Robert A.; Smibert, Craig A; Lipshitz, Howard D.; Boccaccio, Graciela Lidia; Plessis, Anne; Bécam, Isabelle
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
From fly to mammals, the Smaug/Samd4 family of prion-like RNA-binding proteins control gene expression by destabilizing and/or repressing the translation of numerous target transcripts. However, the regulation of its activity remains poorly understood. We show that Smaug's protein levels and mRNA repressive activity are downregulated by Hedgehog signaling in tissue culture cells. These effects rely on the interaction of Smaug with the G-protein coupled receptor Smoothened, which promotes the phosphorylation of Smaug by recruiting the kinase Fused. The activation of Fused and its binding to Smaug are sufficient to suppress its ability to form cytosolic bodies and to antagonize its negative effects on endogenous targets. Importantly, we demonstrate in vivo that HH reduces the levels of smaug mRNA and increases the level of several mRNAs downregulated by Smaug. Finally, we show that Smaug acts as a positive regulator of Hedgehog signaling during wing morphogenesis. These data constitute the first evidence for a post-translational regulation of Smaug and reveal that the fate of several mRNAs bound to Smaug is modulated by a major signaling pathway.
Fil: Bruzzone, Lucia. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
Fil: Argüelles, Camilla. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
Fil: Sanial, Matthieu. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Miled, Samia. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Alvisi, Giorgia. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Gonçalves Antunes, Marina. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Qasrawi, Fairouz. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Holmgren, Robert A.. Northwestern University; Estados Unidos
Fil: Smibert, Craig A. University of Toronto; Canadá
Fil: Lipshitz, Howard D.. University of Toronto; Canadá
Fil: Boccaccio, Graciela Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Plessis, Anne. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
Fil: Bécam, Isabelle. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
Materia
DROSOPHILA
HEDGEHOG
SAMD4
SMAUG
SMOOTHENED
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:11336/211387
Acceder
id CONICETDig_ebe8c664d39633a21f39a31140fee571
oai_identifier_str oai:ri.conicet.gov.ar:11336/211387
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase FusedBruzzone, LuciaArgüelles, CamillaSanial, MatthieuMiled, SamiaAlvisi, GiorgiaGonçalves Antunes, MarinaQasrawi, FairouzHolmgren, Robert A.Smibert, Craig ALipshitz, Howard D.Boccaccio, Graciela LidiaPlessis, AnneBécam, IsabelleDROSOPHILAHEDGEHOGSAMD4SMAUGSMOOTHENEDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1From fly to mammals, the Smaug/Samd4 family of prion-like RNA-binding proteins control gene expression by destabilizing and/or repressing the translation of numerous target transcripts. However, the regulation of its activity remains poorly understood. We show that Smaug's protein levels and mRNA repressive activity are downregulated by Hedgehog signaling in tissue culture cells. These effects rely on the interaction of Smaug with the G-protein coupled receptor Smoothened, which promotes the phosphorylation of Smaug by recruiting the kinase Fused. The activation of Fused and its binding to Smaug are sufficient to suppress its ability to form cytosolic bodies and to antagonize its negative effects on endogenous targets. Importantly, we demonstrate in vivo that HH reduces the levels of smaug mRNA and increases the level of several mRNAs downregulated by Smaug. Finally, we show that Smaug acts as a positive regulator of Hedgehog signaling during wing morphogenesis. These data constitute the first evidence for a post-translational regulation of Smaug and reveal that the fate of several mRNAs bound to Smaug is modulated by a major signaling pathway.Fil: Bruzzone, Lucia. Centre National de la Recherche Scientifique; Francia. Universite de Paris; FranciaFil: Argüelles, Camilla. Centre National de la Recherche Scientifique; Francia. Universite de Paris; FranciaFil: Sanial, Matthieu. Universite de Paris; Francia. Centre National de la Recherche Scientifique; FranciaFil: Miled, Samia. Universite de Paris; Francia. Centre National de la Recherche Scientifique; FranciaFil: Alvisi, Giorgia. Universite de Paris; Francia. Centre National de la Recherche Scientifique; FranciaFil: Gonçalves Antunes, Marina. Universite de Paris; Francia. Centre National de la Recherche Scientifique; FranciaFil: Qasrawi, Fairouz. Universite de Paris; Francia. Centre National de la Recherche Scientifique; FranciaFil: Holmgren, Robert A.. Northwestern University; Estados UnidosFil: Smibert, Craig A. University of Toronto; CanadáFil: Lipshitz, Howard D.. University of Toronto; CanadáFil: Boccaccio, Graciela Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Plessis, Anne. Centre National de la Recherche Scientifique; Francia. Universite de Paris; FranciaFil: Bécam, Isabelle. Centre National de la Recherche Scientifique; Francia. Universite de Paris; FranciaNature Publishing Group2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/211387Bruzzone, Lucia; Argüelles, Camilla; Sanial, Matthieu; Miled, Samia; Alvisi, Giorgia; et al.; Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused; Nature Publishing Group; Embo Reports; 21; 7; 5-2020; 1-161469-221XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.embopress.org/doi/abs/10.15252/embr.201948425info:eu-repo/semantics/altIdentifier/doi/10.15252/embr.201948425info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:25Zoai:ri.conicet.gov.ar:11336/211387instacron: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:34982025-09-29 09:36:25.64CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
title Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
spellingShingle Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
Bruzzone, Lucia
DROSOPHILA
HEDGEHOG
SAMD4
SMAUG
SMOOTHENED
title_short Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
title_full Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
title_fullStr Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
title_full_unstemmed Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
title_sort Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused
dc.creator.none.fl_str_mv Bruzzone, Lucia
Argüelles, Camilla
Sanial, Matthieu
Miled, Samia
Alvisi, Giorgia
Gonçalves Antunes, Marina
Qasrawi, Fairouz
Holmgren, Robert A.
Smibert, Craig A
Lipshitz, Howard D.
Boccaccio, Graciela Lidia
Plessis, Anne
Bécam, Isabelle
author Bruzzone, Lucia
author_facet Bruzzone, Lucia
Argüelles, Camilla
Sanial, Matthieu
Miled, Samia
Alvisi, Giorgia
Gonçalves Antunes, Marina
Qasrawi, Fairouz
Holmgren, Robert A.
Smibert, Craig A
Lipshitz, Howard D.
Boccaccio, Graciela Lidia
Plessis, Anne
Bécam, Isabelle
author_role author
author2 Argüelles, Camilla
Sanial, Matthieu
Miled, Samia
Alvisi, Giorgia
Gonçalves Antunes, Marina
Qasrawi, Fairouz
Holmgren, Robert A.
Smibert, Craig A
Lipshitz, Howard D.
Boccaccio, Graciela Lidia
Plessis, Anne
Bécam, Isabelle
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DROSOPHILA
HEDGEHOG
SAMD4
SMAUG
SMOOTHENED
topic DROSOPHILA
HEDGEHOG
SAMD4
SMAUG
SMOOTHENED
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv From fly to mammals, the Smaug/Samd4 family of prion-like RNA-binding proteins control gene expression by destabilizing and/or repressing the translation of numerous target transcripts. However, the regulation of its activity remains poorly understood. We show that Smaug's protein levels and mRNA repressive activity are downregulated by Hedgehog signaling in tissue culture cells. These effects rely on the interaction of Smaug with the G-protein coupled receptor Smoothened, which promotes the phosphorylation of Smaug by recruiting the kinase Fused. The activation of Fused and its binding to Smaug are sufficient to suppress its ability to form cytosolic bodies and to antagonize its negative effects on endogenous targets. Importantly, we demonstrate in vivo that HH reduces the levels of smaug mRNA and increases the level of several mRNAs downregulated by Smaug. Finally, we show that Smaug acts as a positive regulator of Hedgehog signaling during wing morphogenesis. These data constitute the first evidence for a post-translational regulation of Smaug and reveal that the fate of several mRNAs bound to Smaug is modulated by a major signaling pathway.
Fil: Bruzzone, Lucia. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
Fil: Argüelles, Camilla. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
Fil: Sanial, Matthieu. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Miled, Samia. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Alvisi, Giorgia. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Gonçalves Antunes, Marina. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Qasrawi, Fairouz. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Holmgren, Robert A.. Northwestern University; Estados Unidos
Fil: Smibert, Craig A. University of Toronto; Canadá
Fil: Lipshitz, Howard D.. University of Toronto; Canadá
Fil: Boccaccio, Graciela Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Plessis, Anne. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
Fil: Bécam, Isabelle. Centre National de la Recherche Scientifique; Francia. Universite de Paris; Francia
description From fly to mammals, the Smaug/Samd4 family of prion-like RNA-binding proteins control gene expression by destabilizing and/or repressing the translation of numerous target transcripts. However, the regulation of its activity remains poorly understood. We show that Smaug's protein levels and mRNA repressive activity are downregulated by Hedgehog signaling in tissue culture cells. These effects rely on the interaction of Smaug with the G-protein coupled receptor Smoothened, which promotes the phosphorylation of Smaug by recruiting the kinase Fused. The activation of Fused and its binding to Smaug are sufficient to suppress its ability to form cytosolic bodies and to antagonize its negative effects on endogenous targets. Importantly, we demonstrate in vivo that HH reduces the levels of smaug mRNA and increases the level of several mRNAs downregulated by Smaug. Finally, we show that Smaug acts as a positive regulator of Hedgehog signaling during wing morphogenesis. These data constitute the first evidence for a post-translational regulation of Smaug and reveal that the fate of several mRNAs bound to Smaug is modulated by a major signaling pathway.
publishDate 2020
dc.date.none.fl_str_mv 2020-05
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/11336/211387
Bruzzone, Lucia; Argüelles, Camilla; Sanial, Matthieu; Miled, Samia; Alvisi, Giorgia; et al.; Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused; Nature Publishing Group; Embo Reports; 21; 7; 5-2020; 1-16
1469-221X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/211387
identifier_str_mv Bruzzone, Lucia; Argüelles, Camilla; Sanial, Matthieu; Miled, Samia; Alvisi, Giorgia; et al.; Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused; Nature Publishing Group; Embo Reports; 21; 7; 5-2020; 1-16
1469-221X
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.embopress.org/doi/abs/10.15252/embr.201948425
info:eu-repo/semantics/altIdentifier/doi/10.15252/embr.201948425
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
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score 13.070432

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