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

Integrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the β1 subunit (Itgb1) revealed an alternative functional cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform 578 bp short...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Naipauer, J., Gattelli, A., Degese, M.S., Slomiansky, V., Wertheimer, E., Lamarre, J., Castilla, L., Abba, M., Kordon, E.C., Coso, O.A.
Formato: JOUR
Materias:
Alternative polyadenylation
Gene expression regulation
HuR
Itgb1
Mammary gland
MRNA
beta1 integrin
caspase 3
dactinomycin
HuR protein
microRNA
RNA isoform
short hairpin RNA
article
breast development
cell differentiation
consensus sequence
differentiation
electrophoretic mobility
human
lactation
nonhuman
polyadenylation
priority journal
promoter region
protein binding
protein cleavage
protein expression
protein stability
RNA transcription
Animals
Antigens, CD29
Cell Culture Techniques
Cell Differentiation
Cell Line
Data Mining
Female
Gene Expression Regulation, Developmental
Lactation
Mammary Glands, Animal
Mice
Mice, Inbred BALB C
Polyadenylation
Pregnancy
Recombinant Proteins
RNA Isoforms
RNA Processing, Post-Transcriptional
RNA Stability
RNA, Messenger
RNA, Small Interfering
Specific Pathogen-Free Organisms
Weaning
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_02646021_v454_n2_p345_Naipauer
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Integrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the β1 subunit (Itgb1) revealed an alternative functional cleavage and polyadenylation site that yields a new Itgb1 mRNA isoform 578 bp shorter than that previously reported. 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, where they are differentially regulated at successive developmental stages. The longer mRNA species is prevelant during lactation, whereas the shorter is induced after weaning. In 3D cultures, where expression of integrin β1 protein is required for normal formation of acini, experimental blockade of the longer isoform induced enhanced expression of the shorter species which allowed normal morphological mammary differentiation. The short isoform lacks AU-rich motifs and miRNA target sequences that are potentially implicated in the regulation of mRNA stability and translation efficiency. We further determined that the AU-binding protein HuR appears to selectively stabilize the longer isoform in the mammary gland. In summary, the results of the present study identify a newregulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function. © 2013 Biochemical Society.

Ejemplares similares