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The Role of Exoribonucleases and MutT Pyrophosphohydrolase in the Surveillance of Oxidatively-damaged RNA
Title
The Role of Exoribonucleases and MutT Pyrophosphohydrolase in the Surveillance of Oxidatively-damaged RNA.
Creator
Zhang, Jianan, Li, Zhongwei, Florida Atlantic University
Abstract/Description
Three important exoribonucleases degrading RNAs in sequence-independent manner, RNase II, RNase Rand polynucleotide phosphorylase (PNPase), were shown to protect cells against oxidative stress. This is presumably due to the function of the exoribonucleases in the removal of oxidized RNA in cells. MutT pyrophosphohydrolase .was previously reported to scavenge oxidized nucleotides 8-oxoGTP and 8-oxoGDP, prevent their incorporation into RNA. Deficiency of MutT may lead to an increase in the...
Show moreThree important exoribonucleases degrading RNAs in sequence-independent manner, RNase II, RNase Rand polynucleotide phosphorylase (PNPase), were shown to protect cells against oxidative stress. This is presumably due to the function of the exoribonucleases in the removal of oxidized RNA in cells. MutT pyrophosphohydrolase .was previously reported to scavenge oxidized nucleotides 8-oxoGTP and 8-oxoGDP, prevent their incorporation into RNA. Deficiency of MutT may lead to an increase in the level of 8-oxoG in RNA, which may enhance the requirement of the RNA surveillance function of the exoribonucleases. This study focuses on the roles of the RNA-degradation exoribonucleases in the removal of oxidatively-damaged RNA in the mutT background. This work shows that mutT mutation enhances the sensitivity of the RNase mutants to hydrogen peroxide. Growth defect of the pnp mutT mutant was detected even under normal aeration, but was rescued to the level of pnp mutant under anaerobic conditions. The pnp mutT mutant shows high mutator activity observed from LacZ reporter system and high level of 8-oxoG in RNA, strongly suggest that PNPase is responsible for removing 8-oxoG containing RNAs elevated in mutT background. Additionally, genetic instability observed from the mutant lacking RNase II and MutT supports the idea that RNase II may adopt a distinct pathway to reduce deleterious effect from oxidation challenge.
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Date Issued
2007
PURL
http://purl.flvc.org/fau/fd/FA00000856
Subject Headings
Nucleic acids--Oxidation, DNA repair, Chemical mutagenesis
Format
Document (PDF)
crystallin/sHSP is required for mitochondrial function in human ocular tissue
Title
aB- crystallin/sHSP is required for mitochondrial function in human ocular tissue.
Creator
McGreal, Rebecca., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
The central premise of this dissertation is that the small heat shock protein (sHSP), (Sa(BB-crystallin is essential for lens and retinal pigmented epithelial (RPE) cell function and oxidative stress defense. To date, the mechanism by which it confers protection is not known. We hypothesize that these functions could occur through its ability to protect mitochondrial function in lens and RPE cells. To test this hypothesis, we examined the expression of (Sa(BB-crystallin/sHSP in lens and RPE...
Show moreThe central premise of this dissertation is that the small heat shock protein (sHSP), (Sa(BB-crystallin is essential for lens and retinal pigmented epithelial (RPE) cell function and oxidative stress defense. To date, the mechanism by which it confers protection is not known. We hypothesize that these functions could occur through its ability to protect mitochondrial function in lens and RPE cells. To test this hypothesis, we examined the expression of (Sa(BB-crystallin/sHSP in lens and RPE cells, we observed its localization in the cells, we examined translocation to the mitochondria in these cells upon oxidative stress treatment, we determined its ability to form complexes with and protect cytochrome c (cyt c) against damage, and we observed its ability to preserve mitochondrial function under oxidative stress conditions in lens and RPE cells. In addition to these studies, we examined the effect of mutations of (Sa(BB-crystallin/sHSP on its cellular localization and translocation patterns under oxidative stress, its in vivo and in vitro chaperone activity, and its ability to protect cyt c against oxidation. Our data demonstrated that (Sa(BB-crystallin/sHSP is expressed at high levels in the mitochondria of lens and RPE cells and specifically translocates to the mitochondria under oxidative stress conditions. We demonstrate that (Sa(BB-crystallin/sHSP complexes with cyt c and protects it against oxidative inactivation. Finally, we demonstrate that (Sa(BB-crystallin/sHSP directly protects mitochondria against oxidative inactivation in lens and RPE cells. Since oxidative stress is a key component of lens cataract formation and age-related macular degeneration (AMD), these data provide a new paradigm for understanding the etiology of these diseases.
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Date Issued
2012
PURL
http://purl.flvc.org/FAU/3342242
Subject Headings
Mitochondrial pathology, Chemical mutagenesis, Oxidative stress, Prevention, Cellular signal transduction, Eye, Diseases, Etiology, Molecular chaperones
Format
Document (PDF)