Abstract
Oxidized DNA precursors as well as oxidative DNA lesions seem to contribute to mutagenesis induced by ionizing radiation. Likewise, oxidation of RNA precursors could disturb transduction of correct genetic information encoded in DNA [1]. In this study, we focused on effects of oxidized RNA precursors on RNA produced in in vitro transcription.
We used T7 RNA polymerase as a model enzyme, and 8-hydroxy-GTP (8-OH-GTP) and 2-hydroxy-ATP (2-OH-ATP) as representative oxidized RNA precursors. We analyzed amount of full-length mRNA and nucleotide sequence of the RNA after reverse transcription. We found that (i) addition of 8-OH-GTP and 2-OH-ATP reduced amount of RNA and that (ii) 8-OH-GTP induced T-->G (U-->G) and T-->C (U-->C) mutations, and 2-OH-ATP caused T-->C (U-->C) mutations.
These results suggest that formation of oxidized RNA precursors affects transcription quantitatively and qualitatively, and disturbs expression of correct genetic information.
[1] Taddei et al. Science 278, 128 (1997)
