Relevance of 3´Unstranlated region (3´UTR) in regulation of mRNA beta1 integrin (Itgb1)expression

JULIÁN NAIPAUER 1, ALBANA GATTELLI 1, JONATHAN LAMARRE 2, OMAR COSO 1, EDITH C KORDON 1

Villa Carlos Paz, Córdoba, Argentina.

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008

SAIB

Integrins belong to a super family of cell surface adhesion receptors that play a relevant role during normal development and tumor formation in the mammary gland. We examined gene products of b1 integrin in normal and neoplastic tissue by 3’RACE-PCR. Cloning and sequencing these reaction products, we found a new b1-integrin mRNA species, 578bp shorter than the one previously reported arising from the use of alternative polyadenylation sites. Our analysis also revealed two AU-rich element (ARE) sequences, implicated in the regulation of mRNA levels localized between those sites and, therefore, absent in the shorter mRNA species. We determined that both mRNA forms are present in normal and neoplastic tissue, with a specific ratio corresponding to each physiological condition. We have sub-cloned the corresponding 3’UTR sequences for the two mRNAs into reporter vectors downstream of a CMV driven luciferase gene. Then, mRNA stability assays were performed. The results indicated that the longer form is less stable, suggesting that the ARE sequences may play a relevant role on the stability of this mRNA. Taken together, these data indicate that the presence of alternative 3’UTR regulating sequences may provide another regulatory instance to determine more precisely the b1-integrin abundance required in the different dynamic physiological situations occurring in the mammary gland.