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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2013
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v454_n2_p345_Naipauer http://hdl.handle.net/20.500.12110/paper_02646021_v454_n2_p345_Naipauer |
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paper:paper_02646021_v454_n2_p345_Naipauer2023-06-08T15:23:14Z The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development Degese, Maria Sol Slomiansky, Victoria Wertheimer, Eva Kordon, Edith Claudia Coso, Omar Adrian Alternative polyadenylation Gene expression regulation HuR Itgb1 Mammary gland MRNA beta1 integrin caspase 3 dactinomycin HuR protein microRNA RNA isoform short hairpin RNA article breast development cell differentiation consensus sequence differentiation electrophoretic mobility human lactation nonhuman polyadenylation priority journal promoter region protein binding protein cleavage protein expression protein stability RNA transcription Animals Antigens, CD29 Cell Culture Techniques Cell Differentiation Cell Line Data Mining Female Gene Expression Regulation, Developmental Lactation Mammary Glands, Animal Mice Mice, Inbred BALB C Polyadenylation Pregnancy Recombinant Proteins RNA Isoforms RNA Processing, Post-Transcriptional RNA Stability RNA, Messenger RNA, Small Interfering Specific Pathogen-Free Organisms Weaning 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 newregulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function. © 2013 Biochemical Society. Fil:Degese, M.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Slomiansky, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wertheimer, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kordon, E.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v454_n2_p345_Naipauer http://hdl.handle.net/20.500.12110/paper_02646021_v454_n2_p345_Naipauer |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Alternative polyadenylation Gene expression regulation HuR Itgb1 Mammary gland MRNA beta1 integrin caspase 3 dactinomycin HuR protein microRNA RNA isoform short hairpin RNA article breast development cell differentiation consensus sequence differentiation electrophoretic mobility human lactation nonhuman polyadenylation priority journal promoter region protein binding protein cleavage protein expression protein stability RNA transcription Animals Antigens, CD29 Cell Culture Techniques Cell Differentiation Cell Line Data Mining Female Gene Expression Regulation, Developmental Lactation Mammary Glands, Animal Mice Mice, Inbred BALB C Polyadenylation Pregnancy Recombinant Proteins RNA Isoforms RNA Processing, Post-Transcriptional RNA Stability RNA, Messenger RNA, Small Interfering Specific Pathogen-Free Organisms Weaning |
| spellingShingle |
Alternative polyadenylation Gene expression regulation HuR Itgb1 Mammary gland MRNA beta1 integrin caspase 3 dactinomycin HuR protein microRNA RNA isoform short hairpin RNA article breast development cell differentiation consensus sequence differentiation electrophoretic mobility human lactation nonhuman polyadenylation priority journal promoter region protein binding protein cleavage protein expression protein stability RNA transcription Animals Antigens, CD29 Cell Culture Techniques Cell Differentiation Cell Line Data Mining Female Gene Expression Regulation, Developmental Lactation Mammary Glands, Animal Mice Mice, Inbred BALB C Polyadenylation Pregnancy Recombinant Proteins RNA Isoforms RNA Processing, Post-Transcriptional RNA Stability RNA, Messenger RNA, Small Interfering Specific Pathogen-Free Organisms Weaning Degese, Maria Sol Slomiansky, Victoria Wertheimer, Eva 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 |
Alternative polyadenylation Gene expression regulation HuR Itgb1 Mammary gland MRNA beta1 integrin caspase 3 dactinomycin HuR protein microRNA RNA isoform short hairpin RNA article breast development cell differentiation consensus sequence differentiation electrophoretic mobility human lactation nonhuman polyadenylation priority journal promoter region protein binding protein cleavage protein expression protein stability RNA transcription Animals Antigens, CD29 Cell Culture Techniques Cell Differentiation Cell Line Data Mining Female Gene Expression Regulation, Developmental Lactation Mammary Glands, Animal Mice Mice, Inbred BALB C Polyadenylation Pregnancy Recombinant Proteins RNA Isoforms RNA Processing, Post-Transcriptional RNA Stability RNA, Messenger RNA, Small Interfering Specific Pathogen-Free Organisms Weaning |
| 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 newregulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function. © 2013 Biochemical Society. |
| author |
Degese, Maria Sol Slomiansky, Victoria Wertheimer, Eva Kordon, Edith Claudia Coso, Omar Adrian |
| author_facet |
Degese, Maria Sol Slomiansky, Victoria Wertheimer, Eva Kordon, Edith Claudia Coso, Omar Adrian |
| author_sort |
Degese, Maria Sol |
| 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 |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v454_n2_p345_Naipauer http://hdl.handle.net/20.500.12110/paper_02646021_v454_n2_p345_Naipauer |
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