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
Affiliations
Hongyuan Li
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
Liangping Su
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
Xin Su
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China
Xin Liu
College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China
Dan Wang
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China
Hongmei Li
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China
Xueqing Ba
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China
Yu Zhang
The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China
Jun Lu
The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China
Baiqu Huang
The Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China; Corresponding authors.
Xiaoxue Li
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun 130024, China; Corresponding authors.
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: SKN-1, PRMT-1, Arginine methylation, Oxidative stress
