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

NAIPAUER, JULIAN; GATTELLI, ALBANA; DEGESE, MARIA SOL; SLOMIANSKY, VICTORIA; WERTHEIMER, EVA; LAMARRE, JONATHAN; CASTILLA, LUCIO; ABBA, MARTIN; KORDON, EDITH C.; COSO, OMAR A.

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Año: 2013 vol. 454 p. 345 - 357

0264-6021

Integrins are heterodimeric cell-surface adhesion receptors thatplay a critical role in tissue development. Characterization of thefull-length mRNA encoding the β1 subunit (Itgb1) revealed analternative functional cleavage and polyadenylation site that yieldsa new Itgb1 mRNA isoform 578 bp shorter than that previouslyreported. Using a variety of experimental and bioinformaticapproaches, we found that the two Itgb1 isoforms are expressedat different levels in a variety of mouse tissues, includingthe mammary gland, where they are differentially regulatedat successive developmental stages. The longer mRNA speciesis prevelant during lactation, whereas the shorter is inducedafter weaning. In 3D cultures, where expression of integrin β1protein is required for normal formation of acini, experimentalblockade of the longer isoform induced enhanced expressionof the shorter species which allowed normal morphologicalmammary differentiation. The short isoform lacks AU-rich motifsand miRNA target sequences that are potentially implicated inthe regulation of mRNA stability and translation efficiency. Wefurther determined that the AU-binding protein HuR appears toselectively stabilize the longer isoform in the mammary gland. Insummary, the results of the present study identify a newregulatoryinstance involved in the fine-tuning of Itgb1 expression duringmammary gland development and function.