anticodon and 8-hydroxyguanine

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid β peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

Topics: Amyloid beta-Peptides; Anticodon; Base Pairing; Codon, Nonsense; DNA Repair Enzymes; Gene Knockdown Techniques; Genes, Reporter; Guanine; HeLa Cells; Humans; Luciferases; Mutagenesis; Phosphoric Monoester Hydrolases; Protein Biosynthesis; Reactive Oxygen Species; RNA Interference; RNA, Messenger; RNA, Small Interfering; Transcription, Genetic