Hydrolysis of Bulged Nucleotides in Hybrids Formed by Rna and Imidazole-Derivatized Oligo-2′-O-Methylribonucleotides

Saleh, Anthony; Miller, Paul S.

doi:10.1080/15257770.2011.569810

Cited by 3 publications

(4 citation statements)

References 33 publications

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“…ATM null status was confirmed by phosphorylation assays (May 2009). Adhered cells were irradiated using an Eldorado 8 60 Co teletherapy unit (Theratronics International Ltd) at dose rates between 150 and 180 cGy/min 1 hour before collection, or with 20 J/m 2 of UVB light at 254 nm 1 hour before collection [14] . Cells were treated with 100 µM Etoposide (Sigma-Aldrich) or 50 µM H 2 O 2 (Fisher) 1 hour before collection.…”

Section: Methodsmentioning

confidence: 99%

Cellular Stress Induced Alterations in MicroRNA let-7a and let-7b Expression Are Dependent on p53

et al. 2011

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Genotoxic stressors, such as radiation, induce cellular damage that activates pre-programmed repair pathways, some of which involve microRNAs (miRNA) that alter gene expression. The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However, the role and mechanism underlying regulation of let-7 genes in response to stress have yet to be elucidated. In this study we demonstrate that let-7a and let-7b expression decreases significantly following exposure to agents that induce stress including ionizing radiation. This decrease in expression is dependent on p53 and ATM in vitro and is not observed in a p53−/− colon cancer cell line (HCT116) or ATM−/− human fibroblasts. Chromatin Immunoprecipitation (ChIP) analysis showed p53 binding to a region upstream of the let-7 gene following radiation exposure. Luciferase transient transfections demonstrated that this p53 binding site is necessary for radiation-induced decreases in let-7 expression. A radiation-induced decrease in let-7a and let-7b expression is also observed in radiation-sensitive tissues in vivo and correlates with altered expression of proteins in p53-regulated pro-apoptotic signaling pathways. In contrast, this decreased expression is not observed in p53 knock-out mice suggesting that p53 directly repress let-7 expression. Exogenous expression of let-7a and let-7b increased radiation-induced cytotoxicity in HCT116 p53+/+ cells but not HCT116 p53−/− cells. These results are the first demonstration of a mechanistic connection between the radiation-induced stress response and the regulation of miRNA and radiation-induced cytotoxicity and suggest that this process may be a molecular target for anticancer agents.

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Section: Methodsmentioning

confidence: 99%

Cellular Stress Induced Alterations in MicroRNA let-7a and let-7b Expression Are Dependent on p53

et al. 2011

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“…It has been reported that RNA bulge loop region of an RNA/DNA duplex is susceptible to hydrolysis [10,15,18,19]. We first tested five DNA sequences (DNA 2 , 3 , 4 , 5 and 6 ) for their impact on RNA cleavage rate.…”

Section: Resultsmentioning

confidence: 99%

“…Surprisingly, imidazole, which has been widely used in the design of artificial ribonucleases, showed very low cleaving activity (< 1%). Many artificial ribonucleases as well as the natural RNase A contain a pair of imidazoles to function cooperatively [ 10 , 11 ]. The activity of such a bis-imidazole varies and is highly dependent on the locations and orientations of the two imidazole rings.…”

Section: Resultsmentioning

confidence: 99%

“…After establishing that trans -(±)-cyclohexane-1,2-diamine is the best small molecular catalyst for the cleavage of 1 , we sought to study the influence of the complementary DNA on the cleavage. It has been reported that RNA bulge loop region of an RNA/DNA duplex is susceptible to hydrolysis [ 10 , 15 , 18 , 19 ]. We first tested five DNA sequences (DNA 2 , 3 , 4 , 5 and 6 ) for their impact on RNA cleavage rate.…”

Section: Resultsmentioning

confidence: 99%

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Cleavage of pyrene-stabilized RNA bulge loops by trans-(±)-cyclohexane-1,2-diamine

Patel

Rana

Roy

et al. 2012

Chemistry Central Journal

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Chemical agents that cleave HIV genome can be potentially used for anti-HIV therapy. In this report, the cleavage of the upper stem-loop region of HIV-1 TAR RNA was studied in a variety of buffers containing organic catalysts. trans-(±)-Cyclohexane-1,2-diamine was found to cleave the RNA with the highest activity (31%, 37°C, 18 h). Cleavage of the RNA in trans-(±)-cyclohexane-1,2-diamine buffer was also studied when the RNA was hybridized with complementary DNAs. A pyrene-modified C3 spacer was incorporated to the DNA strand to facilitate the formation of a RNA bulge loop in the RNA/DNA duplex. In contrast, unmodified DNAs cannot efficiently generate RNA bulge loops, regardless of the DNA sequences. The results showed that the pyrene-stablized RNA bulge loops were efficiently and site-specifically cleaved by trans-(±)-cyclohexane-1,2-diamine.

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Crystal structure and physical properties of 1-methyl-3-(carboxymethyl)benzimidazolium betaine·CuBr₂ in crystal and water solution

et al. 2016

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Hydrolysis of Bulged Nucleotides in Hybrids Formed by Rna and Imidazole-Derivatized Oligo-2′-O-Methylribonucleotides

Cited by 3 publications

References 33 publications

Cellular Stress Induced Alterations in MicroRNA let-7a and let-7b Expression Are Dependent on p53

Cellular Stress Induced Alterations in MicroRNA let-7a and let-7b Expression Are Dependent on p53

Cleavage of pyrene-stabilized RNA bulge loops by trans-(±)-cyclohexane-1,2-diamine

Crystal structure and physical properties of 1-methyl-3-(carboxymethyl)benzimidazolium betaine·CuBr₂ in crystal and water solution

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Hydrolysis of Bulged Nucleotides in Hybrids Formed by Rna and Imidazole-Derivatized Oligo-2′-O-Methylribonucleotides

Cited by 3 publications

References 33 publications

Cellular Stress Induced Alterations in MicroRNA let-7a and let-7b Expression Are Dependent on p53

Cellular Stress Induced Alterations in MicroRNA let-7a and let-7b Expression Are Dependent on p53

Cleavage of pyrene-stabilized RNA bulge loops by trans-(±)-cyclohexane-1,2-diamine

Crystal structure and physical properties of 1-methyl-3-(carboxymethyl)benzimidazolium betaine·CuBr2 in crystal and water solution

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Crystal structure and physical properties of 1-methyl-3-(carboxymethyl)benzimidazolium betaine·CuBr₂ in crystal and water solution