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Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation

Human polynucleotide phosphorylase (hPNPase), an exoribonuclease that is primarily localized in mitochondria, plays an important role in reducing oxidized RNA and protecting cells under oxidative stress conditions. hPNPase contains two catalytic domains (RPH1 and RPH2) and two RNA binding domains (K...

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Autores principales: Malla, Sulochan, Li, Zhongwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051052/
https://www.ncbi.nlm.nih.gov/pubmed/32123871
http://dx.doi.org/10.36959/584/448
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author Malla, Sulochan
Li, Zhongwei
author_facet Malla, Sulochan
Li, Zhongwei
author_sort Malla, Sulochan
collection PubMed
description Human polynucleotide phosphorylase (hPNPase), an exoribonuclease that is primarily localized in mitochondria, plays an important role in reducing oxidized RNA and protecting cells under oxidative stress conditions. hPNPase contains two catalytic domains (RPH1 and RPH2) and two RNA binding domains (KH and S1), and an N-terminal mitochondrial translocation signal (MTS). In this study, we examined the potential roles of each domain in hPNPase function on controlling RNA oxidative damage. DNA encoding full-length hPNPase and its domain-deletion mutants were introduced into HeLa cells, and the levels of an oxidized RNA lesion, 8-hydroxyguanosine (8-oxo-Guo) were determined in mitochondrial and cytoplasmic RNA under oxidative stress conditions. Our study showed that the S1 RNA binding domain is crucial for reducing 8-oxo-Guo in both cytoplasm and mitochondria, while the MTS is required for 8-oxo-Guo reduction in mitochondria.
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spelling pubmed-70510522020-03-02 Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation Malla, Sulochan Li, Zhongwei Insights Biomed Res Article Human polynucleotide phosphorylase (hPNPase), an exoribonuclease that is primarily localized in mitochondria, plays an important role in reducing oxidized RNA and protecting cells under oxidative stress conditions. hPNPase contains two catalytic domains (RPH1 and RPH2) and two RNA binding domains (KH and S1), and an N-terminal mitochondrial translocation signal (MTS). In this study, we examined the potential roles of each domain in hPNPase function on controlling RNA oxidative damage. DNA encoding full-length hPNPase and its domain-deletion mutants were introduced into HeLa cells, and the levels of an oxidized RNA lesion, 8-hydroxyguanosine (8-oxo-Guo) were determined in mitochondrial and cytoplasmic RNA under oxidative stress conditions. Our study showed that the S1 RNA binding domain is crucial for reducing 8-oxo-Guo in both cytoplasm and mitochondria, while the MTS is required for 8-oxo-Guo reduction in mitochondria. 2019-09-22 2019 /pmc/articles/PMC7051052/ /pubmed/32123871 http://dx.doi.org/10.36959/584/448 Text en http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Malla, Sulochan
Li, Zhongwei
Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation
title Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation
title_full Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation
title_fullStr Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation
title_full_unstemmed Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation
title_short Functions of Conserved Domains of Human Polynucleotide Phosphorylase on RNA Oxidation
title_sort functions of conserved domains of human polynucleotide phosphorylase on rna oxidation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051052/
https://www.ncbi.nlm.nih.gov/pubmed/32123871
http://dx.doi.org/10.36959/584/448
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