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A Study on the Potential Role of Stress Granules and Processing Bodies in Eliminating Oxidatively Damaged RNA
Title
A Study on the Potential Role of Stress Granules and Processing Bodies in Eliminating Oxidatively Damaged RNA.
Creator
Pourkalbassi, Delaram, Li, Zhongwei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description
Oxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and...
Show moreOxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and processing bodies (PB) in eliminating abasic RNA in situ. We demonstrated that RNA is a major target of oxidative damage, constituting the majority of OS-induced abasic nucleic acids in HeLa cell. Importantly, the level of abasic RNA is strongly correlated with SG abundance. Furthermore, inhibition of SG/PB formation causes accumulation of abasic RNA, suggesting that SG/PB participates in removing oxidized RNA and protects cells under OS, which offers novel targets for therapeutic intervention in age-related diseases.
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FA00004702
Subject Headings
Aging -- Physiological aspects., Oxidative stress., RNA -- Metabolism.
Format
Document (PDF)
RNA oxidative damage and ribosomal RNA surveillance under oxidative stress
Title
RNA oxidative damage and ribosomal RNA surveillance under oxidative stress.
Creator
Liu, Min, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
We have studies oxidative damage of RNA, a major type of cellular macromolecules. RNA is a primary target of reactive oxygen species (ROS). Under oxidative stress, most nucleic acid damages in Escherichia coli (E.coli) are present in RNA as shown by high levels of 8-oxo-G, an oxidized form of guanine. Increased RNA oxidation is closely correlated to cell death under oxidative stress. Surprisingly, neither RNA structure nor association with proteins protects RNA from oxidation... Our results...
Show moreWe have studies oxidative damage of RNA, a major type of cellular macromolecules. RNA is a primary target of reactive oxygen species (ROS). Under oxidative stress, most nucleic acid damages in Escherichia coli (E.coli) are present in RNA as shown by high levels of 8-oxo-G, an oxidized form of guanine. Increased RNA oxidation is closely correlated to cell death under oxidative stress. Surprisingly, neither RNA structure nor association with proteins protects RNA from oxidation... Our results demonstrate a major role for RNA degradation in controlling oxidized RNA. We have identified activities that may work in specific pathways for selectively degrading damaged RNA. These activities may play pivotal rold in controlling oxidized RNA and protecting cells under oxidative stress.
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Date Issued
2012
PURL
http://purl.flvc.org/FAU/3355620
Subject Headings
RNA, Metabolism, Cellular signal transduction, Genetic translation, Molecular biology
Format
Document (PDF)
role for polynucleotide phosphorylase in protecting cells and controlling RNA quality under oxidative stress
Title
A role for polynucleotide phosphorylase in protecting cells and controlling RNA quality under oxidative stress.
Creator
Wu, Jinhua., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
RNA damage occurring under oxidative stress has been shown to cause RNA dysfunction and must be detrimental to cells and organisms. We propose that damaged RNA can be removed by specific RNA surveillance activities. In this work, we investigated the role of polynucleotide phosphorylase (PNPase), a 3'->5' exoribonuclease, in protecting the cells against oxidative stress and eliminating oxidatively-damaged RNA. Previously, it was reported that E. coli PNPase has a higher affinity to poly(8-oxoG...
Show moreRNA damage occurring under oxidative stress has been shown to cause RNA dysfunction and must be detrimental to cells and organisms. We propose that damaged RNA can be removed by specific RNA surveillance activities. In this work, we investigated the role of polynucleotide phosphorylase (PNPase), a 3'->5' exoribonuclease, in protecting the cells against oxidative stress and eliminating oxidatively-damaged RNA. Previously, it was reported that E. coli PNPase has a higher affinity to poly(8-oxoG:A). We further confirmed that E. coli PNPase can specifically bind to an oxidized RNA with a high affinity. An E. coli strain deficient in PNPase (pnp) is hypersensitive to hydrogen peroxide (H2O2). Importantly, the level of H2O2-induced RNA damage, measured by the content of 8-hydroxyguanosine, increases significantly in the pnp mutant cells. Consistent with the notion that PNPase plays a direct role in these processes, introduction of the pnp gene encoding E. coli PNPase can restore the viability and RNA oxidation level of the pnp mutant cells in response to H2O2 treatment. Interestingly, degradosome-association is not required for PNPase to protect cell against oxidative stress. PNPase is evolutionary conserved in most of organisms of all domains of life. The human polynucleotide phosphorylase (hPNPase) localizes mainly in mitochondria and plays pleiotropic roles in cell differentiation and has been previously shown to bind 8- oxoG-RNA with a high affinity. Here we show that similar to E. coli PNPase, hPNPase plays an indispensable role in protecting HeLa cells against oxidative stress. The viability in HeLa cell and 8-oxoG levels in RNA are inversely correlated in response to H2O2- treatment. After removal of oxidative challenge, the elevated level of 8-oxoG in RNA decreases, suggesting the existence of surveillance mechanism(s) for cleaning up oxidized RNA., We have shown that hPNPase may be responsible for the surveillance of oxidized RNA in mammalian cells.Overexpresion of hPNPase reduces RNA oxidation and increases HeLa cell viability against H2O2 insult. Conversely, hPNPase knockdown decreases the viability and increases 8-oxoG level in HeLa cells exposed to H2O2. Taken together, our results suggest that RNA oxidation is a challenging problem for living organisms, and PNPase may play an important role in protecting both prokaryotic and eukaryotic cells by limiting damage to RNA under oxidative stress.
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Date Issued
2008
PURL
http://purl.flvc.org/FAU/186302
Subject Headings
RNA, Metabolism, Biopolymers, Physiological transport, Bacterial genetics, Proteins, Synthesis, Cellular signal transduction
Format
Document (PDF)