Transcriptional Mutagenesis Mediated by 8-oxoG Induces Translational Errors in Mammalian Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 Apr 4

PMID 29610342

Citations 32

Authors

Da-Peng Dai

Wei Gan

Hiroshi Hayakawa

Jia-Lou Zhu

Xiu-Qing Zhang

Guo-Xin Hu

Tao Xu

Zhe-Li Jiang

Li-Qun Zhang

Xue-Da Hu

Ben Nie

Yue Zhou

Jin Li

Xiao-Yang Zhou

Jian Li

Tie-Mei Zhang

Qing He

Dong-Ge Liu

Hai-Bo Chen

Nan Yang

Ping-Ping Zuo

Zhi-Xin Zhang

Huan-Ming Yang

Yao Wang

Samuel H Wilson

Yi-Xin Zeng

Jian-Ye Wang

Mutsuo Sekiguchi

Jian-Ping Cai

Affiliations

Soon will be listed here.

Abstract

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.

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