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AU-rich elements and alternative splicing in the beta-catenin 3'UTR can influence the human beta-catenin mRNA stability.

Thiele, A. and Nagamine, Y. and Hauschildt, S. and Clevers, J.C. (2006) AU-rich elements and alternative splicing in the beta-catenin 3'UTR can influence the human beta-catenin mRNA stability. Experimental cell research, 312(12), 2367-2378. ISSN 00144827. doi: 10.1016/j.yexcr.2006.03.029.

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Abstract

Beta-catenin, the central player of the Wnt signaling cascade, is a well-known oncogene. The regulation of beta-catenin protein stability has been studied extensively while other mechanisms that control cellular levels of beta-catenin have hardly been addressed. In this study, we show that there are three beta-catenin mRNA splice variants that differ solely in their 3'-untranslated region (3'UTR) due to alternative splicing or retaining of an intron. The three isoforms were found to be ubiquitously expressed though in different quantities. Upon induction of the beta-catenin protein in peripheral blood mononuclear leukocytes (PBMC), the beta-catenin mRNA is induced in an isoform-specific manner. All three variants occur in the cytoplasm and contribute to the synthesis of beta-catenin acting as a transcriptional coactivator but have different cytoplasmic stabilities in Hela cells. AU-rich elements (AREs), sequence elements implicated in the regulation of mRNA stability, are found in each of the three transcripts. Surprisingly, the AREs contribute to stabilization of the beta-catenin mRNA transcripts in a splicing-dependent manner. The isoform most affected is the one found to be most induced when beta-catenin protein accumulates. These results suggest that alternative splicing and AREs can act together in regulating beta-catenin mRNA stability and thereby provide a step of controlling the cellular beta-catenin concentration.

Item Type:Article
Additional Information:doi: 10.1016/j.yexcr.2006.03.029
Institutes:Hubrecht Instituut
ID Code:3594
Deposited On:13 Feb 2009 17:14
Last Modified:10 Dec 2009 13:14

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