Battle against RNA oxidation: molecular mechanisms for reducing oxidized RNA to protect cells

Abstract

Oxidation is probably the most common type of damage that occurs in cellular RNA. Oxidized RNA may be dysfunctional and is implicated in the pathogenesis of age-related human diseases. Cellular mechanisms controlling oxidized RNA have begun to be revealed. Currently, a number of ribonucleases and RNA binding proteins have been shown to reduce oxidized RNA and to protect cells under oxidative stress. Although information about how these factors work is still very limited, we suggest several mechanisms that can be used to minimize oxidized RNA in various organisms.

Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains

“…Host nutritional status is a vital component of the body's response to pathogens, as is seen in hospitalized adults with influenza-like illness, in which both underweight and overweight status impacts susceptibility to IAV (23). In work with malnourished mice, Beck et al described heightened host oxidative stress as an influence on mutation rates of RNA viruses, and it is known RNA sustains oxidative damage that may directly impact RdRp fidelity (29,46,47). The obesogenic environment generates high levels of reactive oxygen species (ROS), which may contribute to the distinct evolutionary pressures in the obese state (48,49).…”

Assessment of food toxicology

“…Frequently used models are the mouse lymphoma tk gene mutation assay, the Chinese hamster ovary (CHO) chromosomal aberration assay, the micronucleus clastogenicity assay and the Comet assay [2,6,27]. Interestingly, there has been a high false positive rate (low specificity) in genotoxicity testing which might be due to the recent discovery of non-covalent DNA interaction and interference of toxicants with critical DNA metabolizing proteins such as topoisomerase and DNA polymerases [27,58,[79][80][81]. The linkage between cell-based in vitro, ex vivo and in vivo evaluation is evident by the micronucleus test used for genotoxic screening of chromosomal damage in bone marrow polychromatic erythrocytes [6,124].…”

“…[73][74][75][76] [12,19,24,[77][78][79][80]. Mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage because of the absence of associated histones, an incomplete mitochondrial DNA repair system and the generation of free radicals through electron leakage from the respiratory chain [78][79][80]. Interestingly, carbohydrate oxidation may also be involved in DNA damage, as oxidation and A c c e p t e d M a n u s c r i p t fragmentation of deoxyribose fragments produced from DNA by free-radical attack are believed to play a major role in mutations by blocking the action of DNA polymerase and DNA ligase [19,27,58,81].…”

“…[73][74][75][76] [12,19,24,[77][78][79][80]. Mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage because of the absence of associated histones, an incomplete mitochondrial DNA repair system and the generation of free radicals through electron leakage from the respiratory chain [78][79][80].…”

Translesion Synthesis by MmLV-, AMV-, and HIV-Reverse Transcriptases Using RNA Templates Containing Inosine, Guanosine, and Their 8-oxo-7,8-Dihydropurine Derivatives

“…[14][15][16][17] Oxidized RNA has been shown to occur in various types of RNA including rRNA, 18 miRNA, 19 or mRNA, 20 and intracellular mechanisms in charge of diminishing the impact of oxidation have been reported. [21][22][23][24] Furthermore, the role of oxidative stress on viral pathogenesis 25 is a factor that could lead to interactions between reverse transcriptases and oxidatively damaged RNA. The trend for the oxidation potential of purine nucleobases (I > A > G) 26,27 makes G the likeliest candidate to undergo transformation under oxidative stress.…”