The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development

Autores
Naipauer, Julián; Gatelli, Albana; Degese, María Sol; Slomiansky, Victoria; Wertheimer Hermitte, Eva Victoria; Lamarre, Jonathan; Castilla, Lucio; Abba, Martín Carlos; Kordon, Edith Claudia; Coso, Omar Adrian
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Integrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the β1 subunit (Itgb1) revealed an alternative functional cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform 578 bp shorter than that previously reported. Using a variety of experimental and bioinformatic approaches, we found that the two Itgb1 isoforms are expressed at different levels in a variety of mouse tissues, including the mammary gland, where they are differentially regulated at successive developmental stages. The longer mRNA species is prevelant during lactation, whereas the shorter is induced after weaning. In 3D cultures, where expression of integrin β1 protein is required for normal formation of acini, experimental blockade of the longer isoform induced enhanced expression of the shorter species which allowed normal morphological mammary differentiation. The short isoform lacks AU-rich motifs and miRNA target sequences that are potentially implicated in the regulation of mRNA stability and translation efficiency. We further determined that the AU-binding protein HuR appears to selectively stabilize the longer isoform in the mammary gland. In summary, the results of the present study identify a new regulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function.
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Materia
Bioquímica
Alternative polyadenylation
Gene expression regulation
HuR
Itgbl
Mammary gland
mRNA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/102270

id SEDICI_f3693457bc259b10890b3b0966995759
oai_identifier_str oai:sedici.unlp.edu.ar:10915/102270
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland developmentNaipauer, JuliánGatelli, AlbanaDegese, María SolSlomiansky, VictoriaWertheimer Hermitte, Eva VictoriaLamarre, JonathanCastilla, LucioAbba, Martín CarlosKordon, Edith ClaudiaCoso, Omar AdrianBioquímicaAlternative polyadenylationGene expression regulationHuRItgblMammary glandmRNAIntegrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the β1 subunit (Itgb1) revealed an alternative functional cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform 578 bp shorter than that previously reported. Using a variety of experimental and bioinformatic approaches, we found that the two Itgb1 isoforms are expressed at different levels in a variety of mouse tissues, including the mammary gland, where they are differentially regulated at successive developmental stages. The longer mRNA species is prevelant during lactation, whereas the shorter is induced after weaning. In 3D cultures, where expression of integrin β1 protein is required for normal formation of acini, experimental blockade of the longer isoform induced enhanced expression of the shorter species which allowed normal morphological mammary differentiation. The short isoform lacks AU-rich motifs and miRNA target sequences that are potentially implicated in the regulation of mRNA stability and translation efficiency. We further determined that the AU-binding protein HuR appears to selectively stabilize the longer isoform in the mammary gland. In summary, the results of the present study identify a new regulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function.Centro de Investigaciones Inmunológicas Básicas y Aplicadas2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf345-357http://sedici.unlp.edu.ar/handle/10915/102270enginfo:eu-repo/semantics/altIdentifier/url/https://ri.conicet.gov.ar/11336/13692info:eu-repo/semantics/altIdentifier/url/http://www.biochemj.org/content/454/2/345info:eu-repo/semantics/altIdentifier/issn/1470-8728info:eu-repo/semantics/altIdentifier/doi/10.1042/BJ20130062info:eu-repo/semantics/altIdentifier/hdl/11336/13692info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:20:56Zoai:sedici.unlp.edu.ar:10915/102270Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:20:56.696SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
title The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
spellingShingle The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
Naipauer, Julián
Bioquímica
Alternative polyadenylation
Gene expression regulation
HuR
Itgbl
Mammary gland
mRNA
title_short The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
title_full The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
title_fullStr The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
title_full_unstemmed The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
title_sort The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
dc.creator.none.fl_str_mv Naipauer, Julián
Gatelli, Albana
Degese, María Sol
Slomiansky, Victoria
Wertheimer Hermitte, Eva Victoria
Lamarre, Jonathan
Castilla, Lucio
Abba, Martín Carlos
Kordon, Edith Claudia
Coso, Omar Adrian
author Naipauer, Julián
author_facet Naipauer, Julián
Gatelli, Albana
Degese, María Sol
Slomiansky, Victoria
Wertheimer Hermitte, Eva Victoria
Lamarre, Jonathan
Castilla, Lucio
Abba, Martín Carlos
Kordon, Edith Claudia
Coso, Omar Adrian
author_role author
author2 Gatelli, Albana
Degese, María Sol
Slomiansky, Victoria
Wertheimer Hermitte, Eva Victoria
Lamarre, Jonathan
Castilla, Lucio
Abba, Martín Carlos
Kordon, Edith Claudia
Coso, Omar Adrian
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bioquímica
Alternative polyadenylation
Gene expression regulation
HuR
Itgbl
Mammary gland
mRNA
topic Bioquímica
Alternative polyadenylation
Gene expression regulation
HuR
Itgbl
Mammary gland
mRNA
dc.description.none.fl_txt_mv Integrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the β1 subunit (Itgb1) revealed an alternative functional cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform 578 bp shorter than that previously reported. Using a variety of experimental and bioinformatic approaches, we found that the two Itgb1 isoforms are expressed at different levels in a variety of mouse tissues, including the mammary gland, where they are differentially regulated at successive developmental stages. The longer mRNA species is prevelant during lactation, whereas the shorter is induced after weaning. In 3D cultures, where expression of integrin β1 protein is required for normal formation of acini, experimental blockade of the longer isoform induced enhanced expression of the shorter species which allowed normal morphological mammary differentiation. The short isoform lacks AU-rich motifs and miRNA target sequences that are potentially implicated in the regulation of mRNA stability and translation efficiency. We further determined that the AU-binding protein HuR appears to selectively stabilize the longer isoform in the mammary gland. In summary, the results of the present study identify a new regulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function.
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
description Integrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the β1 subunit (Itgb1) revealed an alternative functional cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform 578 bp shorter than that previously reported. Using a variety of experimental and bioinformatic approaches, we found that the two Itgb1 isoforms are expressed at different levels in a variety of mouse tissues, including the mammary gland, where they are differentially regulated at successive developmental stages. The longer mRNA species is prevelant during lactation, whereas the shorter is induced after weaning. In 3D cultures, where expression of integrin β1 protein is required for normal formation of acini, experimental blockade of the longer isoform induced enhanced expression of the shorter species which allowed normal morphological mammary differentiation. The short isoform lacks AU-rich motifs and miRNA target sequences that are potentially implicated in the regulation of mRNA stability and translation efficiency. We further determined that the AU-binding protein HuR appears to selectively stabilize the longer isoform in the mammary gland. In summary, the results of the present study identify a new regulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/102270
url http://sedici.unlp.edu.ar/handle/10915/102270
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://ri.conicet.gov.ar/11336/13692
info:eu-repo/semantics/altIdentifier/url/http://www.biochemj.org/content/454/2/345
info:eu-repo/semantics/altIdentifier/issn/1470-8728
info:eu-repo/semantics/altIdentifier/doi/10.1042/BJ20130062
info:eu-repo/semantics/altIdentifier/hdl/11336/13692
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
345-357
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1844616084559233024
score 13.070432