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.
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Research Article|
August 09 2013
The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
Julian Naipauer;
Julian Naipauer
1
*LFBM-DFBMC, Departamento de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Buenos Aires C1428EHA, Argentina
†IFIBYNE-CONICET, Buenos Aires, Argentina
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Albana Gattelli;
Albana Gattelli
1
†IFIBYNE-CONICET, Buenos Aires, Argentina
‡LEGMA-DQB, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EHA, Argentina
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Maria Sol Degese;
Maria Sol Degese
*LFBM-DFBMC, Departamento de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Buenos Aires C1428EHA, Argentina
†IFIBYNE-CONICET, Buenos Aires, Argentina
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Victoria Slomiansky;
Victoria Slomiansky
†IFIBYNE-CONICET, Buenos Aires, Argentina
‡LEGMA-DQB, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EHA, Argentina
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Eva Wertheimer;
Eva Wertheimer
§CEFYBO-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina
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Jonathan Lamarre;
Jonathan Lamarre
∥DBMS, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada, N1G 2W1
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Lucio Castilla;
Lucio Castilla
¶Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, U.S.A.
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Martin Abba;
Martin Abba
**CINIBA, Facultad de Ciencias Médicas, Universidad Nacional de La Plata (UNLP), Buenos Aires 1900, Argentina
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Edith C. Kordon;
†IFIBYNE-CONICET, Buenos Aires, Argentina
‡LEGMA-DQB, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EHA, Argentina
3To whom correspondence should be addressed (email ekordon@qb.fcen.uba.ar).
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Omar A. Coso
Omar A. Coso
2
*LFBM-DFBMC, Departamento de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Buenos Aires C1428EHA, Argentina
†IFIBYNE-CONICET, Buenos Aires, Argentina
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Publisher: Portland Press Ltd
Received:
January 10 2013
Revision Received:
June 20 2013
Accepted:
June 21 2013
Accepted Manuscript online:
June 21 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 454 (2): 345–357.
Article history
Received:
January 10 2013
Revision Received:
June 20 2013
Accepted:
June 21 2013
Accepted Manuscript online:
June 21 2013
Citation
Julian Naipauer, Albana Gattelli, Maria Sol Degese, Victoria Slomiansky, Eva Wertheimer, Jonathan Lamarre, Lucio Castilla, Martin Abba, Edith C. Kordon, Omar A. Coso; The use of alternative polyadenylation sites renders integrin β1 (Itgb1) mRNA isoforms with differential stability during mammary gland development. Biochem J 1 September 2013; 454 (2): 345–357. doi: https://doi.org/10.1042/BJ20130062
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