RNA has become a promising target for pharmacological purposes. Most current strategies are directed toward down-regulating its functions. In this study, we provide evidence of the up-regulation of messenger RNA in a sequence-specific manner. The bcl2 (b)-ARE (adenine-uridine-rich element) in the 3'-untranslated region of the b-RNA that regulates the rate of RNA degradation has been targeted with three chemically modified oligoribonucleotides designed in the antisense orientation (asORNs). The three asORNs were studied by a cell-free degradation assay. All three slowed the rate of RNA decay in a dose-response fashion, they were specific to the b-ARE, and two of them were individually effective. asORNs were then transfected into the malignant cells in culture and b-RNA half-life was measured by real-time reverse transcriptase-polymerase chain reaction. We showed that by stabilizing b-RNA the three asORNs increased the expression of b-RNA and of the relevant protein in a dose-response fashion.
Increased Bcl2 expression by antisense oligoribonucleotides targeting the adenine-uridine-rich element motif / L.Ghisolfi; L.Papucci; A.Bevilacqua; G.Canti; G.Tataranni; A.Lapucci; N.Schiavone; S.Capaccioli; A.Nicolin. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - STAMPA. - 68:(2005), pp. 816-821. [10.1124/mol.105.014357]
Increased Bcl2 expression by antisense oligoribonucleotides targeting the adenine-uridine-rich element motif.
PAPUCCI, LAURA;LAPUCCI, ANDREA;SCHIAVONE, NICOLA;CAPACCIOLI, SERGIO;
2005
Abstract
RNA has become a promising target for pharmacological purposes. Most current strategies are directed toward down-regulating its functions. In this study, we provide evidence of the up-regulation of messenger RNA in a sequence-specific manner. The bcl2 (b)-ARE (adenine-uridine-rich element) in the 3'-untranslated region of the b-RNA that regulates the rate of RNA degradation has been targeted with three chemically modified oligoribonucleotides designed in the antisense orientation (asORNs). The three asORNs were studied by a cell-free degradation assay. All three slowed the rate of RNA decay in a dose-response fashion, they were specific to the b-ARE, and two of them were individually effective. asORNs were then transfected into the malignant cells in culture and b-RNA half-life was measured by real-time reverse transcriptase-polymerase chain reaction. We showed that by stabilizing b-RNA the three asORNs increased the expression of b-RNA and of the relevant protein in a dose-response fashion.File | Dimensione | Formato | |
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