左建儒研究组与曹晓风研究组、鲍时来研究组、孔照胜研究组合作研究，发现了在植物应答胁迫的过程中，一氧化氮调控蛋白质甲基化研究的新机制，相关论文于2017年8月17日在Molecular Cell杂志发表(网络版于7月27日发表)，并被该刊选为当期“Featured Article”，配发了题为“Modulating the Modulator: Regulation of Protein Methylation by Nitric Oxide”的专文评述(Preview；http://www.cell.com/molecular-cell/current)。作为该论文的共同第一作者，胡济梁博士和杨焕杰博士日前接受了Molecular Cell杂志Meet the Author专栏的书面采访，讲述了发现背后的故事(http://www.cell.com/molecular-cell/meet-the-author/hu-yang)。
Molecular Cell杂志每期推选一篇“Featured Article”，并书面采访第一作者，旨在鼓励和褒奖青年科学家。
Meet the Author
Jiliang Hu and Huanjie Yang are the first authors of Nitric Oxide Regulates Protein Methylation during Stress Responses in Plants, which appears in the August 17, 2017 issue of Molecular Cell. The authors report that nitric oxide positively regulates the methyltransferase activity of Arabidopsis PRMT5 through S-nitrosylation at Cys-125 during stress responses. S-nitrosylation at Cys-125 enhances the level of Arg symmetric dimethylation, leading to proper splicing-specific pre-mRNA of stress-related genes and eventually boosting the tolerance to stresses.
Jiliang: I grew up in Yiyang City, located in the middle and lower reaches of Yangtze River, Hunan, China. After education at Hunan Agricultural University and Xiangya Medical School of Central South University, I joined Jianru Zuo’s lab at the Institute of Genetics and Developmental Biology (IGDB), Chinese Academy of Sciences (CAS), as a PhD candidate.
Huanjie: I was born in Jining, the hometown of Confucius, a beautiful city in Shandong province, China. I received my bachelor’s degree from Qingdao University. In 2010, I joined the laboratory of Prof. Jianru Zuo at IGDB, CAS and graduated in January 2016. Now I’m a postdoc in the lab.
Jiliang: I have loved plants and animals since I was a kid, and hope to know more about what makes them so diverse.
Huanjie: I love nature and am amazed at the wonderful natural phenomena. So I want to uncover the mysteries of life science.
Jiliang: I got my PhD and post-doctoral training in Jianru Zuo’s lab, and Prof. Zuo’s rigorous scholarship and dedication inspired me a lot.
Huanjie: My mentor Jianru Zuo always encourages me to climb the peak of scientific research when I feel confused about my scientific future.
Jiliang: I like playing table tennis and Tai Chi Chuan, a traditional Chinese physical exercise. Playing makes me relaxed.
Huanjie: I have been practicing yoga for three years. After exercise, I feel relaxed and recharged.
Jiliang: I like sci-fi books and movies, but cannot tell which one is my favorite. I enjoy the novel stories that attract me.
Huanjie: Wolf Totem is one of my favorite books. The Indian movies Three Idiots and Dangal deeply impressed me. When I have time at home, I like making some simple but healthy food.
Jiliang: Alexander Fleming, the discoverer of lysozyme and penicillin, which saved countless lives.
Huanjie: Since I was a middle school student, Marie Sklodowska Curie has become my role model because of her great, selfless contribution to science.
Jiliang: My current goal is to make more discoveries in life science.
Huanjie: To own a botanical garden and culture various plants.
Jiliang: The possible application of our findings from scientific research. I would like my family and friends to know that what I am doing is meaningful.
Huanjie: I tell them that my work aims to know the functions of plant genes and proteins. If the genes or proteins don’t work normally, the plants cannot grow healthily.
Huanjie: I dream of becoming a fitness trainer.
Jiliang: “Where there is a will, there is a way.”
Huanjie: “All is well.”
Jiliang: The work based on my interest could benefit other people.
Huanjie: Be needed by my family and friends.
Jiliang: My first project in Zuo’s lab was to identify novel target proteins regulated by nitric oxide in Arabidopsis by proteomic methods. We obtained hundreds of newly identified S-nitrosylated proteins, and PRMT5 was one of them. The relationship between nitric oxide and epigenetic regulation remained largely unexplored then, so we started with great interest.
Huanjie: Since Jiliang left the lab in September 2015, I started to work on this project, attracted by the altered responses of transgenic plants to salt stress.
Jiliang: Good nitric oxide research foundation had already been laid down in the lab when I started the PRMT5 S-nitrosylation project, especially the cell death-regulating roles of nitric oxide and the S-nitrosylation of phosphotransfer proteins during cytokinin signaling. Hence, we confirmed the S-nitrosylation of PRMT5, characterized the modification sites, and revealed the role of PRMT5 S-nitrosylation in plant salt stress response without too much hindrance. However, we encountered difficulties during further investigation of the molecular mechanisms. We explored many possibilities, and disappointedly revealed that the involvement of PRMT5 S-nitrosylation in salt stress response was not mediated by altering PRMT5 protein translation or subcellular distribution. Through collaboration with Prof. Xiaofeng Cao’s and Shilai Bao’s labs and other researchers, we finally disclosed the function of nitric oxide in regulating PRMT5 enzymatic activity, target protein methylation, and pre-mRNA alternative splicing during plant stress response.
Huanjie: To sort out the article needs patience, and my mentor Jianru Zuo modified the manuscript dozens of times for better presentation.
Jiliang: We experienced many exciting moments during the past years on this project. The most unforgettable moment was the first view of Arabidopsis plants carrying the point mutation of S-nitrosylation site in culture medium. I still clearly remember how we sowed the newly collected seeds, followed by frequent observation nearly every four or five hours.
Huanjie: The moment we received responses from the reviewers.
Both: Immediately after acceptance of the paper, we shared this exciting news with all members that have worked and are still working in our lab. The Wechat group of our lab, a popular social media in China, was full of happiness, congratulations, and excitement. Also, a gathering and discussion is planned during the upcoming National Congress of Plant Biology that will be held in Chongqing, China this November.
Both: We would like to thank our mentor, Prof. Jianru Zuo, for his guidance and inspirational thinking during every stage of the project! Also, thanks go to all the co-authors and lab members!
Both: Current knowledge about protein S-nitrosylation and underlying mechanisms remains limited considering the pleiotropic phenotypes in plants with altered nitric oxide content. For instance, how is the nitric oxide-mediated protein S-nitrosylation in plants involved in regulation of other developmental processes and responses to environmental stresses? The S-nitrosylation of key components of other signaling cascades? Also, the interaction between protein S-nitrosylation and other protein post-translational modifications deserves elaborate investigations under different contexts.
Nitric Oxide Regulates Protein Methylation during Stress Responses in
Jiliang Hu, Huanjie Yang, Jinye Mu, Tiancong Lu, Juli Peng, Xian Deng, Zhaosheng Kong, Shilai Bao, Xiaofeng Cao, Jianru Zuo
Abstract：Methylation and nitric oxide (NO)-based S-nitrosylation are highly conserved protein posttranslational modifications that regulate diverse biological processes. In higher eukaryotes, PRMT5 catalyzes Arg symmetric dimethylation, including key components of the spliceosome. The Arabidopsis prmt5 mutant shows severe developmental defects and impaired stress responses. However, little is known about the mechanisms regulating the PRMT5 activity. Here, we report that NO positively regulates the PRMT5 activity through S-nitrosylation at Cys-125 during stress responses. In prmt5-1 plants, a PRMT5C125S transgene, carrying a non-nitrosylatable mutation at Cys-125, fully rescues the developmental defects, but not the stress hypersensitive phenotype and the responsiveness to NO during stress responses. Moreover, the salt-induced Arg symmetric dimethylation is abolished in PRMT5C125S/prmt5-1 plants, correlated to aberrant splicing of pre-mRNA derived from a stress-related gene. These findings define a mechanism by which plants transduce stress-triggered NO signal to protein methylation machinery through S-nitrosylation of PRMT5 in response to environmental alterations.
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