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

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 short...

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Autores principales: 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
Formato: Articulo
Lenguaje:Inglés
Publicado: 2013
Materias:
HuR
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/102270
https://ri.conicet.gov.ar/11336/13692
http://www.biochemj.org/content/454/2/345
Aporte de:
id I19-R120-10915-102270
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Alternative polyadenylation
Gene expression regulation
HuR
Itgbl
Mammary gland
mRNA
spellingShingle Bioquímica
Alternative polyadenylation
Gene expression regulation
HuR
Itgbl
Mammary gland
mRNA
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
The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
topic_facet Bioquímica
Alternative polyadenylation
Gene expression regulation
HuR
Itgbl
Mammary gland
mRNA
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.
format Articulo
Articulo
author 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_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_sort Naipauer, Julián
title The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
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 use of alternative polyadenylation sites renders integrin β1 (itgb1) mrna isoforms with differential stability during mammary gland development
publishDate 2013
url http://sedici.unlp.edu.ar/handle/10915/102270
https://ri.conicet.gov.ar/11336/13692
http://www.biochemj.org/content/454/2/345
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