The use of alternative poly-adenylation sites renders β1-integrin mRNA species with differential stability during mammary gland development.

NAIPAUER J.; ABBA M; GATTELLI A; DEGESE S.,; LAMARRE J.; COSO O.; KORDON E

Manchester

Congreso; 28th IABCR/Breakthrough Breast Cancer Conference. Stromal-epithelial interactions in breast cancer development and progresión,; 2012

IABCR/Breakthrough

@font-face { font-family: "Arial"; }@font-face { font-family: "Cambria"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0cm 0cm 10pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; } Integrins are heterodimeric membrane receptors that play a critical role in the interaction of mammary cells with the extracellular matrix. Characterization of the full length mRNA coding for Subunit b1 (b1-Integrin or Itgb1) revealed an alternative polyA site in the 3´un-translated region (UTR) that produces an Itgb1 mRNA species shorter than those previously reported. In human and mice existence of this alternative variant was confirmed by 3’RACE PCR. Analysis of mouse SAGE libraries and EST sequences shows that relative expression of each isoform is tissue specific. Particularly in the mammary gland, both species are expressed and the ability of these cells to recognize the proximal poly(A) site was confirmed by using specific reporter constructs. The relative level of each Itgb1 mRNA species varies during mammary cell differentiation in vivo and in cultured cells. This effect could be at least partly due to the distinct stability showed by each mRNA species in proliferating or differentiated HC11 cells. By reporter assays we demonstrate that the alternative Itgb1 3’UTR is involved in stability regulation of these mRNAs. In addition, during mammary differentiation, different protein complexes, which include the AU-binding protein Hu-R that modulates mRNA stability, recognize the AU-rich elements that are only present in the longer Itgb1 species. In summary, our data identify a new instance for controlling Itgb1 expression; mRNA stability regulation could be a relevant response to the successive dramatic changes that the interaction between cells and extracellular matrix suffers during mammary gland development and function.