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 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.
Bevilacqua
Annamaria
A
Department of Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy.
Ghisolfi
Laura
L
Franzi
Sara
S
Maresca
Giovanna
G
Gherzi
Roberto
R
Capaccioli
Sergio
S
Nicolin
Angelo
A
Canti
Gianfranco
G
D000225:Adenine; D001483:Base Sequence; D009843:Oligoribonucleotides / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis*; D015854:Up-Regulation / Q000235:genetics*; D014498:Uracil
D009843:Oligoribonucleotides; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C034537:adenine-uracil dimers; D014498:Uracil; D000225:Adenine