Alternative RNA expression of β1-integrin in different stages of mammary gland development

JULIAN NAIPAUER; ALBANA GATELLI,; MARIA SOL DEGESE; JONATHAN LAMARRE; MARTIN ABBA; EDITH C. KORDON; OMAR A. COSO

Bariloche

Congreso; SISTAM 2012 - The Second South American Spring Symposium in Signal Transduction and Molecular Medicine? (SISTAM2012); 2012

43.- Alternative RNA expression of β1-integrin in different stages of mammary gland development Naipauer J. 1,3, Gattelli A. 2,3, Degese M.S. 1,3, LaMarre J. 4, Abba M. 5, Kordon E. 2,3 and Coso O. 1,3. 1 LFBM - DFBMC, 2 LEGMA - DQB, 3 IFIBYNE - CONICET - FCEN - Univ. de Buenos Aires - ARGENTINA, 4 DBMS, Ontario Veterinary College, Univ. of Guelph, Canada, 5 CINIBA - FCM - Univ. de La Plata - ARGENTINA. Integrins are heterodimeric cell surface adhesion receptors that play a critical role in normal tissue development and tumor formation. Characterization of the full length mRNA encoding the β1 subunit of Integrin (Itgb1) revealed an alternative cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform, 578bp shorter than that previously reported. We determined that this new polyadenylation site is functional in mouse and human cells. 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. Specifically in this tissue, expression of Itgb1 isoforms is differentially regulated at successive developmental stages. The longer mRNA species is higher in differentiated cells both in vivo and in culture, while the shorter species is induced after weaning and in mechanically stressed cells. The newly-described short isoform lacks AU-rich motifs and miRNA target sequences that are potentially implicated in the regulation of mRNA stability and translation efficiency. We determined that the AU binding protein HuR appears to selectively stabilize the longer isoform in the mammary gland. In summary, our data clearly identify a new regulatory instance for controlling Itgb1 expression during mammary gland development and function.