Arginine methylation of SKN-1 promotes oxidative stress resistance in Caenorhabditis elegans

Hongyuan Li; Liangping Su; Xin Su; Xin Liu; Dan Wang; Hongmei Li; Xueqing Ba; Yu Zhang; Jun Lu; Baiqu Huang; Xiaoxue Li

doi:10.1016/j.redox.2019.101111

Arginine methylation of SKN-1 promotes oxidative stress resistance in Caenorhabditis elegans

Redox Biol. 2019 Feb:21:101111. doi: 10.1016/j.redox.2019.101111. Epub 2019 Jan 15.

Authors

Hongyuan Li¹, Liangping Su², Xin Su³, Xin Liu⁴, Dan Wang³, Hongmei Li³, Xueqing Ba³, Yu Zhang⁵, Jun Lu⁵, Baiqu Huang⁶, Xiaoxue Li⁷

Affiliations

¹ The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China; Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
² The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China; School of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China.
³ The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China.
⁴ College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China.
⁵ The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
⁶ The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China. Electronic address: huangbq705@nenu.edu.cn.
⁷ The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China. Electronic address: lixx956@nenu.edu.cn.

Abstract

Caenorhabditis elegans NRF (NF-E2-related factor)/CNC (Cap'n'collar) transcription factor, Skinhead-1 (SKN-1), is conservatively critical for promoting phase II detoxification gene expressions in response to oxidative stress. SKN-1 activity is controlled by well-known phosphorylation and recently-reported O-GlcNAcylation. Whether other kinds of posttanslational modifications of SKN-1 occur and influence its function remains elusive. Here, we found arginines 484 and 516 (R484/R516) of SKN-1 were asymmetrically dimethylated by PRMT-1. Oxidative stress enhanced the binding of PRMT-1 to SKN-1. Consequently, asymmetrical dimethylation of arginines on SKN-1 was elevated. Loss of prmt-1 or disruption of R484/R516 dimethylation decreased the enrichment of SKN-1 on the promoters of SKN-1-driven phase II detoxification genes, including gamma-glutamine cysteine synthetase gcs-1, glutathione S-transferases gst-7 and gst-4, which resulted in reduced ability of worms to defense against oxidative stress. These findings have important implications for investigating the physiological and pathological functions of arginine methylation on conserved NRF/CNC transcription factors in human diseases related to oxidative stress response.

Keywords: Arginine methylation; Oxidative stress; PRMT-1; SKN-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / metabolism
Arginine / metabolism*
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics*
DNA-Binding Proteins / genetics*
Gene Expression Regulation
Metabolic Detoxication, Phase II
Methylation
Models, Biological
Oxidative Stress / genetics*
Promoter Regions, Genetic
Transcription Factors / genetics*

Substances

Antioxidants
Caenorhabditis elegans Proteins
DNA-Binding Proteins
Transcription Factors
skn-1 protein, C elegans
Arginine

Grants and funding

P40 OD010440/OD/NIH HHS/United States