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Unraveling the molecular mechanism of human polynucleotide phosphorylase (hPNPase) in controlling oxidized RNA
| Title: | Unraveling the molecular mechanism of human polynucleotide phosphorylase (hPNPase) in controlling oxidized RNA. |
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| Name(s): |
Malla, Sulochan , author Li, Zhongwei , Thesis advisor Florida Atlantic University, Degree grantor Department of Biomedical Science Charles E. Schmidt College of Science |
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| Type of Resource: | text | |
| Genre: | Electronic Thesis Or Dissertation | |
| Date Created: | 2019 | |
| Date Issued: | 2019 | |
| Publisher: | Florida Atlantic University | |
| Place of Publication: | Boca Raton, Fla. | |
| Physical Form: | application/pdf | |
| Extent: | 159 p. | |
| Language(s): | English | |
| Abstract/Description: | Oxidation by reactive oxygen species is the major source of RNA damaging insult in living organisms. Increased RNA oxidation has been strongly implicated in a wide range of human diseases; predominantly neurodegeneration. Oxidized RNA should be removed from the cellular system to prevent their deleterious effect to the cells and organisms. In eukaryotic cells, mitochondria are the major intracellular sources of ROS and may cause greater damage to the mitochondrial RNA. In this study, we first investigated the RNA oxidation, by measuring the level of 8-hydroxy-Guanosine (8-oxo-Guo), inside mitochondria and cytoplasm in cultured human cells. We discovered that the mitochondrial 8-oxo-Guo is higher than its cytoplasmic counterparts under both normal growth and oxidative stress condition. Next, we explored the role of human polynucleotide phosphorylase (hPNPase) in controlling RNA oxidation inside mitochondria and cytoplasm. hPNPase binds to oxidized RNA with higher affinity, reduces the 8-oxo-Guo level in total RNA and protects cells against oxidative stress. In this study, the molecular mechanism of hPNPase in 8-oxo-Guo reduction was investigated. First, the effect of hPNPase activities on the 8-oxo-Guo level in mitochondria and cytoplasm was examined. The knockdown of hPNPase increased both the mitochondrial and cytoplasmic 8-oxo-Guo, whereas overexpression had the opposite effect. Second, our study revealed that hSUV3, an RNA helicase that forms a functional complex with hPNPase in mitochondria, was dispensable in reducing 8-oxo-Guo levels. | |
| Identifier: | FA00013392 (IID) | |
| Degree granted: | Dissertation (Ph.D.)--Florida Atlantic University, 2019. | |
| Collection: | FAU Electronic Theses and Dissertations Collection | |
| Note(s): | Includes bibliography. | |
| Subject(s): |
RNA Reactive Oxygen Species Mitochondria Oxidative stress |
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| Held by: | Florida Atlantic University Libraries | |
| Sublocation: | Digital Library | |
| Persistent Link to This Record: | http://purl.flvc.org/fau/fd/FA00013392 | |
| Use and Reproduction: | Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder. | |
| Use and Reproduction: | http://rightsstatements.org/vocab/InC/1.0/ | |
| Host Institution: | FAU | |
| Is Part of Series: | Florida Atlantic University Digital Library Collections. |
