Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR

Autores
Cavatorta, Ana Laura; Facciuto, Florencia Natalia; Bugnon Valdano, Marina Paula; Marziali, Federico Emanuel; Giri, Adriana Angelica; Banks, Lawrence; Gardiol, Daniela Nora
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Human Disc large (DLG1) has been demonstrated to be involved in thecontrol of cell polarity and maintenance of tissue architecture, and is fre-quently lost in human tumours. However, the mechanisms controllingDLG1 expression are poorly understood. To further examine the regulationof DLG1 expression, we analysed the 5¢ ends of DLG1 transcripts by rapidamplification of cDNA ends polymerase chain reaction. We identified analternative splicing event in the 5¢ region of DLG1 mRNA that generatestranscripts with two different 5¢ untranslated regions (5¢-UTRs). We showby reporter assays that the DLG1 5¢-UTR containing an alternativelyspliced exon interferes with the translation of a downstream open readingframe (ORF). However, no significant differences in mRNA stabilityamong the DLG1 5¢-UTR variants were observed. Sequence analysis of theadditional exon present in the larger DLG1 5¢-UTR showed the presenceof an upstream short ORF which is lost in the short version of the 5¢-UTRDLG1. By mutagenesis and luciferase assays, we analysed the contributionof this upstream short ORF in reducing translation efficiency, and showedthat its disruption can revert, to some extent, the negative regulation oflarge 5¢-UTR. Using computational modelling we also show that the largeDLG1 5¢-UTR isoform forms a more stable structure than the short ver-sion, and this may contribute to its ability to repress translation. This rep-resents the first analysis of the 5¢ region of the DLG1 transcripts andshows that differential expression of alternatively spliced 5¢-UTRs with dif-ferent translational properties could result in changes in DLG1 abundance.
Fil: Cavatorta, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Facciuto, Florencia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Bugnon Valdano, Marina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Marziali, Federico Emanuel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Giri, Adriana Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Banks, Lawrence. No especifíca;
Fil: Gardiol, Daniela Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Materia
cancer
DLG1
polarity
translation regulation
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:11336/278098
Acceder
id CONICETDig_dd7840c023767d4a351e8016ad2143a5
oai_identifier_str oai:ri.conicet.gov.ar:11336/278098
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTRCavatorta, Ana LauraFacciuto, Florencia NataliaBugnon Valdano, Marina PaulaMarziali, Federico EmanuelGiri, Adriana AngelicaBanks, LawrenceGardiol, Daniela NoracancerDLG1polaritytranslation regulationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Human Disc large (DLG1) has been demonstrated to be involved in thecontrol of cell polarity and maintenance of tissue architecture, and is fre-quently lost in human tumours. However, the mechanisms controllingDLG1 expression are poorly understood. To further examine the regulationof DLG1 expression, we analysed the 5¢ ends of DLG1 transcripts by rapidamplification of cDNA ends polymerase chain reaction. We identified analternative splicing event in the 5¢ region of DLG1 mRNA that generatestranscripts with two different 5¢ untranslated regions (5¢-UTRs). We showby reporter assays that the DLG1 5¢-UTR containing an alternativelyspliced exon interferes with the translation of a downstream open readingframe (ORF). However, no significant differences in mRNA stabilityamong the DLG1 5¢-UTR variants were observed. Sequence analysis of theadditional exon present in the larger DLG1 5¢-UTR showed the presenceof an upstream short ORF which is lost in the short version of the 5¢-UTRDLG1. By mutagenesis and luciferase assays, we analysed the contributionof this upstream short ORF in reducing translation efficiency, and showedthat its disruption can revert, to some extent, the negative regulation oflarge 5¢-UTR. Using computational modelling we also show that the largeDLG1 5¢-UTR isoform forms a more stable structure than the short ver-sion, and this may contribute to its ability to repress translation. This rep-resents the first analysis of the 5¢ region of the DLG1 transcripts andshows that differential expression of alternatively spliced 5¢-UTRs with dif-ferent translational properties could result in changes in DLG1 abundance.Fil: Cavatorta, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Facciuto, Florencia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Bugnon Valdano, Marina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Marziali, Federico Emanuel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Giri, Adriana Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Banks, Lawrence. No especifíca;Fil: Gardiol, Daniela Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaWiley Blackwell Publishing, Inc2011-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278098Cavatorta, Ana Laura; Facciuto, Florencia Natalia; Bugnon Valdano, Marina Paula; Marziali, Federico Emanuel; Giri, Adriana Angelica; et al.; Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR; Wiley Blackwell Publishing, Inc; Febs Journal; 278; 14; 5-2011; 2596-26081742-464XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2011.08188.xinfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1742-4658.2011.08188.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:15:09Zoai:ri.conicet.gov.ar:11336/278098instacron: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:34982025-12-23 13:15:09.45CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
title Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
spellingShingle Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
Cavatorta, Ana Laura
cancer
DLG1
polarity
translation regulation
title_short Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
title_full Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
title_fullStr Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
title_full_unstemmed Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
title_sort Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR
dc.creator.none.fl_str_mv Cavatorta, Ana Laura
Facciuto, Florencia Natalia
Bugnon Valdano, Marina Paula
Marziali, Federico Emanuel
Giri, Adriana Angelica
Banks, Lawrence
Gardiol, Daniela Nora
author Cavatorta, Ana Laura
author_facet Cavatorta, Ana Laura
Facciuto, Florencia Natalia
Bugnon Valdano, Marina Paula
Marziali, Federico Emanuel
Giri, Adriana Angelica
Banks, Lawrence
Gardiol, Daniela Nora
author_role author
author2 Facciuto, Florencia Natalia
Bugnon Valdano, Marina Paula
Marziali, Federico Emanuel
Giri, Adriana Angelica
Banks, Lawrence
Gardiol, Daniela Nora
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv cancer
DLG1
polarity
translation regulation
topic cancer
DLG1
polarity
translation regulation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Human Disc large (DLG1) has been demonstrated to be involved in thecontrol of cell polarity and maintenance of tissue architecture, and is fre-quently lost in human tumours. However, the mechanisms controllingDLG1 expression are poorly understood. To further examine the regulationof DLG1 expression, we analysed the 5¢ ends of DLG1 transcripts by rapidamplification of cDNA ends polymerase chain reaction. We identified analternative splicing event in the 5¢ region of DLG1 mRNA that generatestranscripts with two different 5¢ untranslated regions (5¢-UTRs). We showby reporter assays that the DLG1 5¢-UTR containing an alternativelyspliced exon interferes with the translation of a downstream open readingframe (ORF). However, no significant differences in mRNA stabilityamong the DLG1 5¢-UTR variants were observed. Sequence analysis of theadditional exon present in the larger DLG1 5¢-UTR showed the presenceof an upstream short ORF which is lost in the short version of the 5¢-UTRDLG1. By mutagenesis and luciferase assays, we analysed the contributionof this upstream short ORF in reducing translation efficiency, and showedthat its disruption can revert, to some extent, the negative regulation oflarge 5¢-UTR. Using computational modelling we also show that the largeDLG1 5¢-UTR isoform forms a more stable structure than the short ver-sion, and this may contribute to its ability to repress translation. This rep-resents the first analysis of the 5¢ region of the DLG1 transcripts andshows that differential expression of alternatively spliced 5¢-UTRs with dif-ferent translational properties could result in changes in DLG1 abundance.
Fil: Cavatorta, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Facciuto, Florencia Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Bugnon Valdano, Marina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Marziali, Federico Emanuel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Giri, Adriana Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Banks, Lawrence. No especifíca;
Fil: Gardiol, Daniela Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
description Human Disc large (DLG1) has been demonstrated to be involved in thecontrol of cell polarity and maintenance of tissue architecture, and is fre-quently lost in human tumours. However, the mechanisms controllingDLG1 expression are poorly understood. To further examine the regulationof DLG1 expression, we analysed the 5¢ ends of DLG1 transcripts by rapidamplification of cDNA ends polymerase chain reaction. We identified analternative splicing event in the 5¢ region of DLG1 mRNA that generatestranscripts with two different 5¢ untranslated regions (5¢-UTRs). We showby reporter assays that the DLG1 5¢-UTR containing an alternativelyspliced exon interferes with the translation of a downstream open readingframe (ORF). However, no significant differences in mRNA stabilityamong the DLG1 5¢-UTR variants were observed. Sequence analysis of theadditional exon present in the larger DLG1 5¢-UTR showed the presenceof an upstream short ORF which is lost in the short version of the 5¢-UTRDLG1. By mutagenesis and luciferase assays, we analysed the contributionof this upstream short ORF in reducing translation efficiency, and showedthat its disruption can revert, to some extent, the negative regulation oflarge 5¢-UTR. Using computational modelling we also show that the largeDLG1 5¢-UTR isoform forms a more stable structure than the short ver-sion, and this may contribute to its ability to repress translation. This rep-resents the first analysis of the 5¢ region of the DLG1 transcripts andshows that differential expression of alternatively spliced 5¢-UTRs with dif-ferent translational properties could result in changes in DLG1 abundance.
publishDate 2011
dc.date.none.fl_str_mv 2011-05
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/11336/278098
Cavatorta, Ana Laura; Facciuto, Florencia Natalia; Bugnon Valdano, Marina Paula; Marziali, Federico Emanuel; Giri, Adriana Angelica; et al.; Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR; Wiley Blackwell Publishing, Inc; Febs Journal; 278; 14; 5-2011; 2596-2608
1742-464X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278098
identifier_str_mv Cavatorta, Ana Laura; Facciuto, Florencia Natalia; Bugnon Valdano, Marina Paula; Marziali, Federico Emanuel; Giri, Adriana Angelica; et al.; Regulation of translational efficiency by different splice variants of the Disc large 1 oncosuppressor 5′‐UTR; Wiley Blackwell Publishing, Inc; Febs Journal; 278; 14; 5-2011; 2596-2608
1742-464X
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://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2011.08188.x
info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1742-4658.2011.08188.x
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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