Oxidative Stress Induced by Arsenite is Involved in YTHDF2 Phase Separation
Jin Man1, Qian Zhang1, Tianhe Zhao1
1Department of Environmental and Occupational Health, West China School of Public Health, Sichuan University, Chengdu, 610041, Sichuan, China.
Biological Trace Element Research
|June 13, 2023
Summary
Arsenite exposure induces oxidative stress, promoting YTHDF2 phase separation and altering N-methyladenosine (m6A) levels. Antioxidant N-acetylcysteine reverses these effects, highlighting oxidative stress
Area of Science:
- Molecular Biology
- Cell Biology
- Toxicology
Background:
- YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) phase separation is observed upon arsenite stimulation.
- Oxidative stress is a primary mechanism of arsenite toxicity.
- The role of arsenite-induced oxidative stress in YTHDF2 phase separation requires elucidation.
Purpose of the Study:
- To investigate the impact of arsenite-induced oxidative stress on YTHDF2 phase separation.
- To determine the involvement of N-methyladenosine (m6A) modification in this process.
Main Methods:
- Human keratinocytes were exposed to varying concentrations of sodium arsenite and the antioxidant N-acetylcysteine.
- Levels of oxidative stress, YTHDF2 phase separation, and m6A modification were quantified.
- Changes in m6A methylesterase and demethylase levels were analyzed.
Main Results:
- Arsenite exposure increased oxidative stress and YTHDF2 phase separation in a dose-dependent manner.
- N-acetylcysteine pretreatment attenuated arsenite-induced oxidative stress and inhibited YTHDF2 phase separation.
- Arsenite exposure elevated m6A levels, upregulated m6A methylesterase, and downregulated m6A demethylases, effects reversed by N-acetylcysteine.
Conclusions:
- Oxidative stress induced by arsenite is a key driver of YTHDF2 phase separation.
- Arsenite-induced YTHDF2 phase separation is mediated by m6A modification.
- This study offers novel insights into arsenite toxicity mechanisms from a phase-separation perspective.
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