RT Journal Article
SR Electronic
T1 Stabilization of Cellular mRNAs and Up-Regulation of Proteins by Oligoribonucleotides Homologous to the Bcl2 Adenine-Uridine Rich Element Motif
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 531
OP 538
DO 10.1124/mol.106.029041
VO 71
IS 2
A1 Annamaria Bevilacqua
A1 Laura Ghisolfi
A1 Sara Franzi
A1 Giovanna Maresca
A1 Roberto Gherzi
A1 Sergio Capaccioli
A1 Angelo Nicolin
A1 Gianfranco Canti
YR 2007
UL http://molpharm.aspetjournals.org/content/71/2/531.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics