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First published on October 31, 2006; DOI: 10.1124/mol.106.029041

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Received for publication July 31, 2006.
Revised October 12, 2006.
Accepted for publication October 31, 2006.

Stabilization of cellular mRNAs and upregulation of proteins by oligoribonucleotides homologous to the Bcl2 ARE motif

Annamaria Bevilacqua 1, Laura Ghisolfi 1, Sara Franzi 1, Giovanna Maresca 1, Roberto Gherzi 2, Sergio Capaccioli 3, Angelo Nicolin 1*, Gianfranco Canti 1

1 Department of Pharmacology - University of Milan 2 Gene Transfer Laboratory, IST 3 Department of Experimental Pathology and Oncology - University of Florence

* Address correspondence to: E-mail: angelo.nicolin{at}unimi.it

Abstract

A-U Rich Elements (ARE) play an important role in modulating mRNA stability, being the target site of many ARE-binding proteins (AUBPs) that are involved in the decay process. Three 26mer 2'O-methyl oligoribonucleotides (ORNs) homologous to the core region of ARE of bcl2 mRNA have been studied for decoy-aptamer activity in UV cross-linking assays. Sense-oriented ORNs competed with the ARE motif for the interaction with both destabilizing and stabilizing AUBPs in cell free systems and in cell lines. Moreover, ORNs induced mRNA stabilization and upregulated both Bcl2 mRNA and protein levels in the cells. Bcl2 ORNs stabilized other ARE-containing transcripts and upregulated their expression. These results indicate that Bcl2 ORNs compete for AUBP-ARE interactions independently of ARE class and suggest that in the cell the default labile status of ARE-containing mRNAs depends on the combined interaction of such transcripts with destabilizing AUBPs.


Key words: Regulation of gene expression, Regulation - post-transcriptional, Overexpression, RNA/siRNA, Oncogenes


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L. Papucci, E. Witort, A. M. Bevilacqua, M. Donnini, M. Lulli, E. Borchi, K. S. A. Khabar, A. Tempestini, A. Lapucci, N. Schiavone, et al.
Impact of Targeting the Adenine- and Uracil-Rich Element of bcl-2 mRNA with Oligoribonucleotides on Apoptosis, Cell Cycle, and Neuronal Differentiation in SHSY-5Y Cells
Mol. Pharmacol., February 1, 2008; 73(2): 498 - 508.
[Abstract] [Full Text] [PDF]


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