INVESTIGADORES
KORDON Edith Claudia
congresos y reuniones científicas
Título:
The use of alternative poly-adenylation sites renders β1-integrin mRNA species with differential stability during mammary gland development.
Autor/es:
NAIPAUER J.; ABBA M; GATTELLI A; DEGESE S.,; LAMARRE J.; COSO O.; KORDON E
Lugar:
Manchester
Reunión:
Congreso; 28th IABCR/Breakthrough Breast Cancer Conference. Stromal-epithelial interactions in breast cancer development and progresión,; 2012
Institución organizadora:
IABCR/Breakthrough
Resumen:
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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 3RACE 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 3UTR 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.