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

0026-895X/07/7102-531-538$20.00
Mol Pharmacol 71:531-538, 2007

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Stabilization of Cellular mRNAs and Up-Regulation of Proteins by Oligoribonucleotides Homologous to the Bcl2 Adenine-Uridine Rich Element MotifFormula

Annamaria Bevilacqua, Laura Ghisolfi, Sara Franzi, Giovanna Maresca, Roberto Gherzi, Sergio Capaccioli, Angelo Nicolin, and Gianfranco Canti

Department of Pharmacology, University of Milan, Milan, Italy (A.B., L.G., S.F., G.M., A.N., G.C.); Gene Transfer Laboratory, IST, Genoa, Italy (R.G.); and Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy (S.C.)

Adenine-uridine rich elements (AREs) 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 26-mer 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 up-regulated both Bcl2 mRNA and protein levels in the cells. Bcl2 ORNs stabilized other ARE-containing transcripts and up-regulated 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.

Received July 30, 2006; accepted October 31, 2006

Address correspondence to: Dr. Angelo Nicolin, Department of Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. E-mail: angelo.nicolin{at}unimi.it




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[Abstract] [Full Text] [PDF]


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