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The use of alternative polyadenylation sites renders integrin beta1 (Itgb1) mRNA isoforms with differential stability during mammary gland development
Authors
Naipauer, JulianGattelli, Albana
Degese, Maria Sol
Slomiansky, Victoria
Wertheimer, Eva
LaMarre, Jonathan
Castilla, Lucio H.
Abba, Martin
Kordon, Edith C.
Coso, Omar A.
UMass Chan Affiliations
Program in Gene Function and ExpressionDocument Type
Journal ArticlePublication Date
2013-09-01Keywords
AnimalsAntigens, 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
RNA Isoforms
*RNA Processing, Post-Transcriptional
*RNA Stability
RNA, Messenger
RNA, Small Interfering
Recombinant Proteins
Specific Pathogen-Free Organisms
Weaning
Biochemistry
Metadata
Show full item recordAbstract
Integrins are heterodimeric cell-surface adhesion receptors that play a critical role in tissue development. Characterization of the full-length mRNA encoding the beta1 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 beta1 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 new regulatory instance involved in the fine-tuning of Itgb1 expression during mammary gland development and function.Source
Biochem J. 2013 Sep 1;454(2):345-57. doi: 10.1042/BJ20130062. Link to article on publisher's siteDOI
10.1042/BJ20130062Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30321PubMed ID
23789592Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1042/BJ20130062