Abstract
Ribonucleic acid (RNA) molecules can be easily attacked by reactive oxygen species (ROS), which are produced during normal cellular metabolism and under various oxidative stress conditions. Numerous findings report that the amount of cellular 8-oxoG, the most abundant RNA damage biomarker, is a promising target for the sensitive measurement of oxidative stress and aging-associated diseases, including neuropsychiatric disorders. Most importantly, available data suggest that RNA oxidation has important implications for various signaling pathways and gene expression regulation in aging-related diseases, highlighting the necessity of using combinations of RNA oxidation adducts in both experimental studies and clinical trials. In this review, we primarily describe evidence for the effect of oxidative stress on RNA integrity modulation and possible quality control systems. Additionally, we discuss the profiles and clinical implications of RNA oxidation products that have been under intensive investigation in several aging-associated medical disorders.
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References
Aas PA, et al. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003;421:859–63. https://doi.org/10.1038/nature01363.
Abe T, Tohgi H, Isobe C, Murata T, Sato C. Remarkable increase in the concentration of 8-hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer’s disease. Journal of Neuroscience Research. 2002;70:447–50. https://doi.org/10.1002/jnr.10349.
Abe T, Isobe C, Murata T, Sato C, Tohgi H (2003) Alteration of 8-hydroxyguanosine concentrations in the cerebrospinal fluid and serum from patients with Parkinson’s disease Neuroscience Letters 336:105-108 doi:https://doi.org/10.1016/s0304-3940(02)01259-4.
Amaya-Montoya M, Perez-Londono A, Guatibonza-Garcia V, Vargas-Villanueva A, Mendivil CO. Cellular senescence as a therapeutic target for age-related diseases: a review advances in therapy. 2020;37:1407–24. https://doi.org/10.1007/s12325-020-01287-0.
Anbara H, Shahrooz R, Razi M, Malekinejad H, Najafi G. The effect of vitamin C on mice hemolytic anemia induced by phenylhydrazine: an animal model study using histological changes in testis, pre-implantation embryo development, and biochemical changes. Iranian Journal of Basic Medical Sciences. 2018;21:668–77. https://doi.org/10.22038/IJBMS.2018.25819.6356.
Antoniali G, Malfatti MC, Tell G. Unveiling the non-repair face of the base excision repair pathway in RNA processing: a missing link between DNA repair and gene expression? DNA Repair. 2017a;56:65–74. https://doi.org/10.1016/j.dnarep.2017.06.008.
Antoniali G, et al. Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nature Communications. 2017b;8:797. https://doi.org/10.1038/s41467-017-00842-8.
Bellacosa A, Moss EG. RNA repair: damage control. Current Biology: CB. 2003;13:R482–4. https://doi.org/10.1016/s0960-9822(03)00408-1.
Benameur L, Charif N, Li Y, Stoltz JF, de Isla N. Toward an understanding of mechanism of aging-induced oxidative stress in human mesenchymal stem cells. Bio-medical Materials and Engineering. 2015;25:41–6. https://doi.org/10.3233/BME-141247.
Bisht S, Faiq M, Tolahunase M, Dada R. Oxidative stress and male infertility. Nature Reviews Urology. 2017;14:470–85. https://doi.org/10.1038/nrurol.2017.69.
Broedbaek K, et al. Urinary markers of nucleic acid oxidation and long-term mortality of newly diagnosed type 2 diabetic patients. Diabetes Care. 2011;34:2594–6. https://doi.org/10.2337/dc11-1620.
Brown NC, Andreazza AC, Young LT. An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Research. 2014;218:61–8. https://doi.org/10.1016/j.psychres.2014.04.005.
Burroughs AM, Aravind L. RNA damage in biological conflicts and the diversity of responding RNA repair systems. Nucleic Acids Research. 2016;44:8525–55. https://doi.org/10.1093/nar/gkw722.
Cadet J, Wagner JR (2013) DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation Cold Spring Harbor Perspectives in Biology 5 doi:https://doi.org/10.1101/cshperspect.a012559
Calabretta A, Kupfer PA, Leumann CJ. The effect of RNA base lesions on mRNA translation. Nucleic Acids Research. 2015;43:4713–20. https://doi.org/10.1093/nar/gkv377.
Calcinotto A, Kohli J, Zagato E, Pellegrini L, Demaria M, Alimonti A. Cellular senescence: aging. Cancer, and Injury Physiological Reviews. 2019;99:1047–78. https://doi.org/10.1152/physrev.00020.2018.
Cameron TA, Matz LM, Sinha D, De Lay NR. Polynucleotide phosphorylase promotes the stability and function of Hfq-binding sRNAs by degrading target mRNA-derived fragments. Nucleic Acids Research. 2019;47:8821–37. https://doi.org/10.1093/nar/gkz616.
Castellani RJ, Nunomura A, Rolston RK, Moreira PI, Takeda A, Perry G, et al. Sublethal RNA oxidation as a mechanism for neurodegenerative disease. International Journal of Molecular Sciences. 2008;9:789–806. https://doi.org/10.3390/ijms9050789.
Cejvanovic V, et al. Iron induced RNA-oxidation in the general population and in mouse tissue. Free Radical Biology & Medicine. 2018a;115:127–35. https://doi.org/10.1016/j.freeradbiomed.2017.11.013.
Cejvanovic V, Kjaer LK, Morup Bergholdt HK, Henriksen T, Weimann A, Ellervik C, et al. RNA oxidation and iron levels in patients with diabetes. Free Radical Biology & Medicine. 2018b;129:532–6. https://doi.org/10.1016/j.freeradbiomed.2018.10.420.
Chang Y, Kong Q, Shan X, Tian G, Ilieva H, Cleveland DW, et al. Messenger RNA oxidation occurs early in disease pathogenesis and promotes motor neuron degeneration in ALS. PloS one. 2008;3:e2849. https://doi.org/10.1371/journal.pone.0002849.
Csiszar A, et al. Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research. GeroScience. 2019;41:209–27. https://doi.org/10.1007/s11357-019-00064-4.
Dai DP, et al. Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells, Proceedings of the National Academy of Sciences of the United States of America. 2018;115:4218–22. https://doi.org/10.1073/pnas.1718363115.
De Luca G, et al. Prolonged lifespan with enhanced exploratory behavior in mice overexpressing the oxidized nucleoside triphosphatase hMTH1. Aging Cell. 2013;12:695–705. https://doi.org/10.1111/acel.12094.
Feyzi E, et al. RNA base damage and repair. Current Pharmaceutical Biotechnology. 2007;8:326–31. https://doi.org/10.2174/138920107783018363.
Fimognari C. Role of oxidative RNA damage in chronic-degenerative diseases. Oxidative Medicine and Cellular Longevity. 2015;2015:358713. https://doi.org/10.1155/2015/358713.
Fimognari C, Lenzi M, Sestili P, Turrini E, Ferruzzi L, Hrelia P, et al. Sulforaphane potentiates RNA damage induced by different xenobiotics. PloS one. 2012;7:e35267. https://doi.org/10.1371/journal.pone.0035267.
Fragopoulou E, et al. Suppression of DNA/RNA and protein oxidation by dietary supplement which contains plant extracts and vitamins: a randomized, double-blind, placebo-controlled trial. Lipids in Health and Disease. 2018;17:187. https://doi.org/10.1186/s12944-018-0836-z.
Freudenthal BD, Beard WA, Perera L, Shock DD, Kim T, Schlick T, et al. Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide. Nature. 2015;517:635–9. https://doi.org/10.1038/nature13886.
Gaillard H, Aguilera A. A novel class of mRNA-containing cytoplasmic granules are produced in response to UV-irradiation. Molecular Biology of the Cell. 2008;19:4980–92. https://doi.org/10.1091/mbc.E08-02-0193.
Gao X, et al. Investigation on potential associations of oxidatively generated DNA/RNA damage with lung, colorectal, breast, prostate and total cancer incidence. Scientific Reports. 2019;9:7109. https://doi.org/10.1038/s41598-019-42596-x.
Gill I, Kaur S, Kaur N, Dhiman M, Mantha AK. Phytochemical Ginkgolide B attenuates amyloid-beta1-42 induced oxidative damage and altered cellular responses in human neuroblastoma SH-SY5Y cells. Journal of Alzheimer’s Disease: JAD. 2017;60:S25–40. https://doi.org/10.3233/JAD-161086.
Golzarroshan B, Lin CL, Li CL, Yang WZ, Chu LY, Agrawal S, et al. Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities. Nucleic Acids Research. 2018;46:8630–40. https://doi.org/10.1093/nar/gky642.
Gong X, Tao R, Li Z. Quantification of RNA damage by reverse transcription polymerase chain reactions. Analytical Biochemistry. 2006;357:58–67. https://doi.org/10.1016/j.ab.2006.06.025.
Gordon AJ, Satory D, Wang M, Halliday JA, Golding I, Herman C. Removal of 8-oxo-GTP by MutT hydrolase is not a major contributor to transcriptional fidelity. Nucleic Acids Research. 2014;42:12015–26. https://doi.org/10.1093/nar/gku912.
Haberle V, Stark A. Eukaryotic core promoters and the functional basis of transcription initiation. Nature Reviews Molecular Cell Biology. 2018;19:621–37. https://doi.org/10.1038/s41580-018-0028-8.
Hayakawa H, Sekiguchi M. Human polynucleotide phosphorylase protein in response to oxidative stress. Biochemistry. 2006;45:6749–55. https://doi.org/10.1021/bi052585l.
Hayakawa H, Kuwano M, Sekiguchi M. Specific binding of 8-oxoguanine-containing RNA to polynucleotide phosphorylase protein. Biochemistry. 2001;40:9977–82. https://doi.org/10.1021/bi010595q.
Hayakawa H, Fujikane A, Ito R, Matsumoto M, Nakayama KI, Sekiguchi M. Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress. Biochemical and Biophysical Research Communications. 2010;403:220–4. https://doi.org/10.1016/j.bbrc.2010.11.011.
Henriksen T, Hillestrom PR, Poulsen HE, Weimann A. Automated method for the direct analysis of 8-oxo-guanosine and 8-oxo-2′-deoxyguanosine in human urine using ultraperformance liquid chromatography and tandem mass spectrometry. Free Radical Biology & Medicine. 2009;47:629–35. https://doi.org/10.1016/j.freeradbiomed.2009.06.002.
Hofer T, Seo AY, Prudencio M, Leeuwenburgh C. A method to determine RNA and DNA oxidation simultaneously by HPLC-ECD: greater RNA than DNA oxidation in rat liver after doxorubicin administration. Biological Chemistry. 2006;387:103–11. https://doi.org/10.1515/BC.2006.014.
Hofer T, et al. Increased iron content and RNA oxidative damage in skeletal muscle with aging and disuse atrophy. Experimental Gerontology. 2008;43:563–70. https://doi.org/10.1016/j.exger.2008.02.007.
Hosseini M, Roy P, Sissler M, Zirbel CL, Westhof E, Leontis N. How to fold and protect mitochondrial ribosomal RNA with fewer guanines. Nucleic Acids Research. 2018;46:10946–68. https://doi.org/10.1093/nar/gky762.
Huber KV, et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature. 2014;508:222–7. https://doi.org/10.1038/nature13194.
Hudson BH, Zaher HS (2015) O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity Rna 21:1648-1659 doi:https://doi.org/10.1261/rna.052464.115.
Ishii T, Sekiguchi M. Two ways of escaping from oxidative RNA damage: Selective degradation and cell death. DNA Repair. 2019;81:102666. https://doi.org/10.1016/j.dnarep.2019.102666.
Ishii T, Hayakawa H, Sekiguchi T, Adachi N, Sekiguchi M. Role of Auf1 in elimination of oxidatively damaged messenger RNA in human cells. Free Radical Biology & Medicine. 2015;79:109–16. https://doi.org/10.1016/j.freeradbiomed.2014.11.018.
Ishii T, Hayakawa H, Igawa T, Sekiguchi T, Sekiguchi M. Specific binding of PCBP1 to heavily oxidized RNA to induce cell death. Proceedings of the National Academy of Sciences of the United States of America. 2018;115:6715–20. https://doi.org/10.1073/pnas.1806912115.
Isobe C, Abe T, Terayama Y. Homocysteine may contribute to pathogenesis of RNA damage in brains with Alzheimer’s disease. Neuro-degenerative Diseases. 2009;6:252–7. https://doi.org/10.1159/000262443.
Jacoby AS, Vinberg M, Poulsen HE, Kessing LV, Munkholm K. Increased DNA and RNA damage by oxidation in patients with bipolar I disorder. Translational Psychiatry. 2016;6:e867. https://doi.org/10.1038/tp.2016.141.
Jang S, et al. Damage sensor role of UV-DDB during base excision repair. Nature Structural & Molecular Biology. 2019;26:695–703. https://doi.org/10.1038/s41594-019-0261-7.
Jemth AS, et al. MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP. Nucleic Acids Research. 2018;46:10888–904. https://doi.org/10.1093/nar/gky896.
Joergensen A, Broedbaek K, Weimann A, Semba RD, Ferrucci L, Joergensen MB, et al. Association between urinary excretion of cortisol and markers of oxidatively damaged DNA and RNA in humans. PloS one. 2011;6:e20795. https://doi.org/10.1371/journal.pone.0020795.
Jorgensen A, et al. Increased systemic oxidatively generated DNA and RNA damage in schizophrenia. Psychiatry Research. 2013a;209:417–23. https://doi.org/10.1016/j.psychres.2013.01.033.
Jorgensen A, et al. Systemic oxidatively generated DNA/RNA damage in clinical depression: associations to symptom severity and response to electroconvulsive therapy. Journal of Affective Disorders. 2013b;149:355–62. https://doi.org/10.1016/j.jad.2013.02.011.
Jorgensen A, Siersma V, Davidsen AS, Weimann A, Henriksen T, Poulsen HE, et al. Markers of DNA/RNA damage from oxidation as predictors of a registry-based diagnosis of psychiatric illness in type 2 diabetic patients. Psychiatry Research. 2018a;259:370–6. https://doi.org/10.1016/j.psychres.2017.11.017.
Jorgensen A, et al. Progressive DNA and RNA damage from oxidation after aneurysmal subarachnoid haemorrhage in humans. Free Radical Research. 2018b;52:51–6. https://doi.org/10.1080/10715762.2017.1407413.
Kim C, Kang D, Lee EK, Lee JS. Long noncoding RNAs and RNA-binding proteins in oxidative stress, cellular senescence, and age-related diseases. Oxidative Medicine and Cellular Longevity. 2017;2017:2062384–21. https://doi.org/10.1155/2017/2062384.
Kournoutou GG, Giannopoulou PC, Sazakli E, Leotsinidis M, Kalpaxis DL. Oxidative damage of 18S and 5S ribosomal RNA in digestive gland of mussels exposed to trace metals. Aquatic Toxicology. 2017;192:136–47. https://doi.org/10.1016/j.aquatox.2017.09.007.
Kuhnel H, et al. Investigations into cytotoxic effects of the herbal preparation abnormal Savda Munziq. Chinese Journal of Integrative Medicine. 2015. https://doi.org/10.1007/s11655-015-2132-3.
Kupfer PA, Leumann CJ. Synthesis, base pairing properties and trans-lesion synthesis by reverse transcriptases of oligoribonucleotides containing the oxidatively damaged base 5-hydroxycytidine. Nucleic Acids Research. 2011;39:9422–32. https://doi.org/10.1093/nar/gkr673.
Li X, Fu XD. Chromatin-associated RNAs as facilitators of functional genomic interactions. Nature Reviews Genetics. 2019;20:503–19. https://doi.org/10.1038/s41576-019-0135-1.
Liguori I, et al. Oxidative stress, aging, and diseases. Clinical Interventions in Aging. 2018;13:757–72. https://doi.org/10.2147/CIA.S158513.
Lin YT, Liu W, He Y, Wu YL, Chen WN, Lin XJ, et al. Hepatitis B virus X protein increases 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-Oxodg) level via repressing MTH1/MTH2 expression in hepatocytes. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2018;51:80–96. https://doi.org/10.1159/000495166.
Liu J, Atamna H, Kuratsune H, Ames BN. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Annals of the New York Academy of Sciences. 2002a;959:133–66. https://doi.org/10.1111/j.1749-6632.2002.tb02090.x.
Liu J, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proceedings of the National Academy of Sciences of the United States of America. 2002b;99:2356–61. https://doi.org/10.1073/pnas.261709299.
Liu X et al. (2016) Elevated levels of urinary markers of oxidative DNA and RNA damage in type 2 diabetes with complications Oxidative Medicine and Cellular Longevity 2016:4323198 doi:https://doi.org/10.1155/2016/4323198.
Liu N, et al. Vitexin compound 1, a novel extraction from a Chinese herb, suppresses melanoma cell growth through DNA damage by increasing ROS levels. Journal of Experimental & Clinical Cancer Research: CR. 2018;37:269. https://doi.org/10.1186/s13046-018-0897-x.
Lovell MA, Soman S, Bradley MA. Oxidatively modified nucleic acids in preclinical Alzheimer’s disease (PCAD) brain. Mechanisms of Ageing and Development. 2011;132:443–8. https://doi.org/10.1016/j.mad.2011.08.003.
Manini P, et al. Biomarkers of nucleic acid oxidation, polymorphism in, and expression of, hOGG1 gene in styrene-exposed workers. Toxicology Letters. 2009;190:41–7. https://doi.org/10.1016/j.toxlet.2009.06.862.
Marie C, Ravanat JL, Badouard C, Marques M, Balducci F, Maitre A. Urinary levels of oxidative DNA and RNA damage among workers exposed to polycyclic aromatic hydrocarbons in silicon production: comparison with 1-hydroxypyrene. Environmental and Molecular Mutagenesis. 2009;50:88–95. https://doi.org/10.1002/em.20439.
Martinet W, De Meyer GR, Herman AG, Kockx MM. RNA damage in human atherosclerosis: pathophysiological significance and implications for gene expression studies. RNA Biology. 2005;2:4–7. https://doi.org/10.4161/rna.2.1.1430.
Mazzoni C, D’Addario I, Falcone C. The C-terminus of the yeast Lsm4p is required for the association to P-bodies. FEBS Letters. 2007:581, 4836–4840. https://doi.org/10.1016/j.febslet.2007.09.009.
Memar MY, Ghotaslou R, Samiei M, Adibkia K. Antimicrobial use of reactive oxygen therapy: current insights. Infection and Drug Resistance. 2018;11:567–76. https://doi.org/10.2147/IDR.S142397.
Millan MJ. Linking deregulation of non-coding RNA to the core pathophysiology of Alzheimer’s disease: an integrative review. Progress in Neurobiology. 2017;156:1–68. https://doi.org/10.1016/j.pneurobio.2017.03.004.
Minas A, Najafi G, Jalali AS, Razi M. Fennel induces cytotoxic effects against testicular germ cells in mice; evidences for suppressed pre-implantation embryo development. Environmental Toxicology. 2018. https://doi.org/10.1002/tox.22570.
Molavi M, Razi M, Malekinejad H, Amniattalab A, Rezaie H. Vitamin E improved cypermethrin-induced damages in the ovary of rats; evidence for angiogenesis and p53 involvement. Pesticide Biochemistry and Physiology. 2014;110:27–35. https://doi.org/10.1016/j.pestbp.2014.02.004.
Mroczek S, Kufel J. Apoptotic signals induce specific degradation of ribosomal RNA in yeast. Nucleic Acids Research. 2008;36:2874–88. https://doi.org/10.1093/nar/gkm1100.
Munkholm K, Poulsen HE, Kessing LV, Vinberg M. Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in bipolar disorder. Bipolar Disorders. 2015;17:257–68. https://doi.org/10.1111/bdi.12245.
Nabavi SM, Habtemariam S, Daglia M, Braidy N, Loizzo MR, Tundis R, et al. Neuroprotective effects of Ginkgolide B against ischemic stroke: a review of current literature. Current Topics in Medicinal Chemistry. 2015;15:2222–32. https://doi.org/10.2174/1568026615666150610142647.
Nandakumar J, Schwer B, Schaffrath R, Shuman S. RNA repair: an antidote to cytotoxic eukaryal RNA damage. Molecular Cell. 2008;31:278–86. https://doi.org/10.1016/j.molcel.2008.05.019.
Newton DL, et al. Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents. Critical Reviews in Oncology/Hematology. 2001;39:79–86. https://doi.org/10.1016/s1040-8428(01)00116-0.
Nie B, et al. Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues. Oxidative Medicine and Cellular Longevity. 2013, 2013;303181. https://doi.org/10.1155/2013/303181.
Nunomura A, et al. Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease. Neurobiology of Disease. 2004;17:108–13. https://doi.org/10.1016/j.nbd.2004.06.003.
Nunomura A, Hofer T, Moreira PI, Castellani RJ, Smith MA, Perry G. RNA oxidation in Alzheimer disease and related neurodegenerative disorders. Acta Neuropathologica. 2009;118:151–66. https://doi.org/10.1007/s00401-009-0508-1.
Nunomura A, Moreira PI, Castellani RJ, Lee HG, Zhu X, Smith MA, et al. Oxidative damage to RNA in aging and neurodegenerative disorders. Neurotoxicity Research. 2012a;22:231–48. https://doi.org/10.1007/s12640-012-9331-x.
Nunomura A, et al. The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. Journal of Neuropathology and experimental Neurology. 2012b;71:233–41. https://doi.org/10.1097/NEN.0b013e318248e614.
Nunomura A, Lee HG, Zhu X, Perry G. Consequences of RNA oxidation on protein synthesis rate and fidelity: implications for the pathophysiology of neuropsychiatric disorders. Biochemical Society Transactions. 2017;45:1053–66. https://doi.org/10.1042/BST20160433.
Nunoshiba T, Ishida R, Sasaki M, Iwai S, Nakabeppu Y, Yamamoto K. A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae. Nucleic Acids Research. 2004;32:5339–48. https://doi.org/10.1093/nar/gkh868.
Ou C, et al. Targeting YAP1/LINC00152/FSCN1 signaling Axis prevents the progression of colorectal cancer. Advanced Science. 2019;1901380. https://doi.org/10.1002/advs.201901380.
Palermo V, Falcone C, Calvani M, Mazzoni C. Acetyl-L-carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fission. Aging Cell. 2010;9:570–9. https://doi.org/10.1111/j.1474-9726.2010.00587.x.
Poulsen HE, et al. Oxidatively generated modifications to nucleic acids in vivo: measurement in urine and plasma. Free Radical Biology & Medicine. 2019;145:336–41. https://doi.org/10.1016/j.freeradbiomed.2019.10.001.
Qiao Z, Wigginton KR. Direct and Indirect photochemical reactions in viral RNA measured with RT-qPCR and mass spectrometry. Environmental Science & Technology. 2016;50:13371–9. https://doi.org/10.1021/acs.est.6b04281.
Rasmussen ST, et al. Simvastatin and oxidative stress in humans: a randomized, double-blinded, placebo- clinical trial controlled. Redox Biology. 2016;9:32–8. https://doi.org/10.1016/j.redox.2016.05.007.
Schmid M, Jensen TH. Controlling nuclear RNA levels. Nature Reviews Genetics. 2018;19:518–29. https://doi.org/10.1038/s41576-018-0013-2.
Schottker B, Xuan Y, Gao X, Anusruti A, Brenner H. Oxidatively damaged DNA/RNA and 8-Isoprostane levels are associated with the development of type 2 diabetes at older age: results from a large cohort study. Diabetes Care. 2020;43:130–6. https://doi.org/10.2337/dc19-1379.
Scott DD, et al. Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA metabolism. Nucleic Acids Research. 2017;45:12509–28. https://doi.org/10.1093/nar/gkx963.
Sekiguchi T, Ito R, Hayakawa H, Sekiguchi M. Elimination and utilization of oxidized guanine nucleotides in the synthesis of RNA and its precursors. The Journal of Biological Chemistry. 2013;288:8128–35. https://doi.org/10.1074/jbc.M112.418723.
Sen A, Hongpaisan J. Hippocampal microvasculature changes in association with oxidative stress in Alzheimer’s disease. Free Radical Biology & Medicine. 2018;120:192–203. https://doi.org/10.1016/j.freeradbiomed.2018.03.034.
Sen A, Nelson TJ, Alkon DL, Hongpaisan J (2018) Loss in PKC epsilon causes downregulation of MnSOD and BDNF expression in neurons of Alzheimer’s disease hippocampus Journal of Alzheimer’s Disease: JAD 63:1173–1189 doi:https://doi.org/10.3233/JAD-171008.
Sheth U, Parker R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science. 2003;300:805–8. https://doi.org/10.1126/science.1082320.
Simms CL, Zaher HS. Quality control of chemically damaged. RNA Cellular and Molecular Life Sciences: CMLS. 2016;73:3639–53. https://doi.org/10.1007/s00018-016-2261-7.
Singh N, Savanur MA, Srivastava S, D'Silva P, Mugesh G. A redox modulatory Mn3 O4 nanozyme with multi-enzyme activity provides efficient cytoprotection to human cells in a Parkinson’s disease model. Angewandte Chemie. 2017;56:14267–71. https://doi.org/10.1002/anie.201708573.
Song XN, et al. Oxidative damage to RNA and expression patterns of MTH1 in the hippocampi of senescence-accelerated SAMP8 mice and Alzheimer’s disease patients. Neurochemical Research. 2011;36:1558–65. https://doi.org/10.1007/s11064-011-0484-4.
Sova H, Jukkola-Vuorinen A, Puistola U, Kauppila S, Karihtala P. 8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer. British Journal of Cancer. 2010;102:1018–23. https://doi.org/10.1038/sj.bjc.6605565.
Stirpe M, Palermo V, Ferrari M, Mroczek S, Kufel J, Falcone C, et al. Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants. Apoptosis: an International Journal on Programmed Cell Death. 2017;22:200–6. https://doi.org/10.1007/s10495-016-1319-1.
Stone CM, et al. Inhibition of homologous phosphorolytic ribonucleases by citrate may represent an evolutionarily conserved communicative link between RNA degradation and central metabolism. Nucleic Acids Research. 2017;45:4655–66. https://doi.org/10.1093/nar/gkx114.
Taddei F, Hayakawa H, Bouton M, Cirinesi A, Matic I, Sekiguchi M, et al. Counteraction by MutT protein of transcriptional errors caused by oxidative damage. Science. 1997;278:128–30. https://doi.org/10.1126/science.278.5335.128.
Takagi Y, Setoyama D, Ito R, Kamiya H, Yamagata Y, Sekiguchi M. Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2. The Journal Of Biological Chemistry. 2012;287:21541–9. https://doi.org/10.1074/jbc.M112.363010.
Teixeira D, Sheth U, Valencia-Sanchez MA, Brengues M, Parker R. Processing bodies require RNA for assembly and contain nontranslating mRNAs. Rna. 2005;11:371–82. https://doi.org/10.1261/rna.7258505.
Tomaszewska-Antczak A, Guga P, Nawrot B, Pratviel G. Guanosine in a single stranded region of anticodon stem-loop tRNA models is prone to oxidatively generated damage resulting in dehydroguanidinohydantoin and spiroiminodihydantoin lesions. Chemistry. 2015;21:6381–5. https://doi.org/10.1002/chem.201406409.
Utumatwishima JN, Chung ST, Bentley AR, Udahogora M, Sumner AE. Reversing the tide - diagnosis and prevention of T2DM in populations of African descent. Nature Reviews Endocrinology. 2018;14:45–56. https://doi.org/10.1038/nrendo.2017.127.
Vascotto C, et al. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Molecular and Cellular Biology. 2009;29:1834–54. https://doi.org/10.1128/MCB.01337-08.
Violet M, Delattre L, Tardivel M, Sultan A, Chauderlier A, Caillierez R, et al. A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions. Frontiers in Cellular Neuroscience. 2014;8:84. https://doi.org/10.3389/fncel.2014.00084.
Violet M, et al. Prefibrillar tau oligomers alter the nucleic acid protective function of tau in hippocampal neurons in vivo. Neurobiology of Disease. 2015;82:540–51. https://doi.org/10.1016/j.nbd.2015.09.003.
Wang JX, et al. Oxidative modification of miR-184 enables it to target Bcl-xL and Bcl-w. Molecular Cell. 2015a;59:50–61. https://doi.org/10.1016/j.molcel.2015.05.003.
Wang WX, Luo SB, Xia MM, Mao YH, Zhou XY, Jiang P, et al. Analysis of the oxidative damage of DNA, RNA, and their metabolites induced by hyperglycemia and related nephropathy in Sprague Dawley rats. Free Radical Research. 2015b;49:1199–209. https://doi.org/10.3109/10715762.2015.1033416.
Wang P, et al. Mapping spatial transcriptome with light-activated proximity-dependent RNA labeling. Nature Chemical Biology. 2019;15:1110–9. https://doi.org/10.1038/s41589-019-0368-5.
Willi J, Kupfer P, Evequoz D, Fernandez G, Katz A, Leumann C, et al. Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center. Nucleic Acids Research. 2018;46:1945–57. https://doi.org/10.1093/nar/gkx1308.
Wu J, Li Z. Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress. Biochemical and Biophysical Research Communications. 2008;372:288–92. https://doi.org/10.1016/j.bbrc.2008.05.058.
Wu J, Jiang Z, Liu M, Gong X, Wu S, Burns CM, et al. Polynucleotide phosphorylase protects Escherichia coli against oxidative stress. Biochemistry. 2009;48:2012–20. https://doi.org/10.1021/bi801752p.
Wurtmann EJ, Wolin SL. RNA under attack: cellular handling of RNA damage. Critical reviews in Biochemistry and Molecular Biology. 2009;44:34–49. https://doi.org/10.1080/10409230802594043.
Yan LL, Zaher HS. How do cells cope with RNA damage and its consequences? J Biol Chem. 2019;294:15158–71. https://doi.org/10.1074/jbc.REV119.006513.
Yan LL, Simms CL, McLoughlin F, Vierstra RD, Zaher HS. Oxidation and alkylation stresses activate ribosome-quality control. Nature Communications. 2019a;10:5611. https://doi.org/10.1038/s41467-019-13579-3.
Yan Y, Chen X, Wang X, Zhao Z, Hu W, Zeng S, et al. The effects and the mechanisms of autophagy on the cancer-associated fibroblasts in cancer. Journal of Experimental & Clinical Cancer Research: CR. 2019b;38:171. https://doi.org/10.1186/s13046-019-1172-5.
Yan Y, et al. Novel function of lncRNA ADAMTS9-AS2 in promoting temozolomide resistance in glioblastoma via Upregulating the FUS/MDM2 ubiquitination axis. Frontiers in Cell and Developmental Biology. 2019c;7:217. https://doi.org/10.3389/fcell.2019.00217.
Yang H, Villani RM, Wang H, Simpson MJ, Roberts MS, Tang M, et al. The role of cellular reactive oxygen species in cancer chemotherapy. Journal of Experimental & Clinical Cancer Research: CR. 2018;37:266. https://doi.org/10.1186/s13046-018-0909-x.
Yarasi S, McConachie C, Loppnow GR. Molecular beacon probes of photodamage in thymine and uracil oligonucleotides. Photochemistry and Photobiology. 2005;81:467–73. https://doi.org/10.1562/2004-09-02-RA-301.
Yoshimura K, Ogawa T, Ueda Y, Shigeoka S. AtNUDX1, an 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate pyrophosphohydrolase, is responsible for eliminating oxidized nucleotides in Arabidopsis. Plant & Cell Physiology. 2007;48:1438–49. https://doi.org/10.1093/pcp/pcm112.
Youn JY, Dyakov BJA, Zhang J, Knight JDR, Vernon RM, Forman-Kay JD, et al. Properties of Stress granule and P-body proteomes. Molecular Cell. 2019;76:286–94. https://doi.org/10.1016/j.molcel.2019.09.014.
Zheng JD, et al. Age-related alterations in the expression of MTH2 in the hippocampus of the SAMP8 mouse with learning and memory deterioration. Journal of the Neurological Sciences. 2009;287:188–96. https://doi.org/10.1016/j.jns.2009.07.027.
Zhou Y, Yao Y, Shao Y, Qu W, Chen Y, Jiang Q. Urinary bisphenol analogues concentrations and biomarkers of oxidative DNA and RNA damage in Chinese school children in East China: a repeated measures study. Environmental Pollution. 2019;254:112921. https://doi.org/10.1016/j.envpol.2019.07.089.
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This work was supported by the National Natural Science Foundation of China (81703036, 81803035), the China Postdoctoral Science Foundation (2017M610510), and the Natural Science Foundation of Hunan Province, China (2019JJ50932).
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Conception and design: ZJ Xu, JZ Huang, M Gao, GJ Guo, SS Zeng, X Chen, X Wang, and ZC Gong. Writing, review, and/or revision of the manuscript: ZJ Xu and YL Yan. Administrative, technical, or material support: X Wang and SS Zeng.
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Xu, Z., Huang, J., Gao, M. et al. Current perspectives on the clinical implications of oxidative RNA damage in aging research: challenges and opportunities. GeroScience 43, 487–505 (2021). https://doi.org/10.1007/s11357-020-00209-w
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DOI: https://doi.org/10.1007/s11357-020-00209-w