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.
Stabilization of cellular mRNAs and upregulation of proteins by oligoribonucleotides homologous to the Bcl2 adenine-uridine rich motif / A.BEVILACQUA; L.GHISOLFI; S.FRANZI; G.MARESCA; R.GHERZI; S.CAPACCIOLI; A.NICOLIN; G.CANTI. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - STAMPA. - 71:(2007), pp. 531-538. [10.1124/mol.106.029041]
Stabilization of cellular mRNAs and upregulation of proteins by oligoribonucleotides homologous to the Bcl2 adenine-uridine rich motif
CAPACCIOLI, SERGIO;
2007
Abstract
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.File | Dimensione | Formato | |
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