Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells

Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):4218-4222. doi: 10.1073/pnas.1718363115. Epub 2018 Apr 2.


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.

Keywords: 8-oxoG; MTH1; RNA oxidization; amyloid β peptides.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / genetics
  • Anticodon / genetics
  • Base Pairing
  • Codon, Nonsense
  • DNA Repair Enzymes / antagonists & inhibitors
  • DNA Repair Enzymes / genetics
  • Gene Knockdown Techniques
  • Genes, Reporter
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • HeLa Cells
  • Humans
  • Luciferases / genetics
  • Mutagenesis / genetics*
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors
  • Phosphoric Monoester Hydrolases / genetics
  • Protein Biosynthesis / genetics*
  • RNA Interference
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Reactive Oxygen Species
  • Transcription, Genetic / genetics*


  • Amyloid beta-Peptides
  • Anticodon
  • Codon, Nonsense
  • RNA, Messenger
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • 8-hydroxyguanine
  • Guanine
  • Luciferases
  • Phosphoric Monoester Hydrolases
  • 8-oxodGTPase
  • DNA Repair Enzymes