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

Adenine- uridine rich elements ( AREs) play an important role in modulating mRNA stability, being the target site of many AREbinding 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 AREcontaining 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.