Stabilization of cellular mRNAs and up-regulation of proteins by oligoribonucleotides homologous to the Bcl2 adenine-uridine rich element motif

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)531-538
Number of pages8
JournalMolecular Pharmacology
Volume71
Issue number2
DOIs
Publication statusPublished - Feb 2007

ASJC Scopus subject areas

  • Pharmacology

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