研究方向
与DNA和组蛋白上表观遗传修饰类似,RNA上也存在动态可逆的化学修饰(如首个被我们发现的可逆RNA修饰N6-甲基腺嘌呤),对RNA加工代谢具有重要的调控功能从而影响基因表达,进而调控一系列重要的生命活动过程和疾病的发生发展。这一新兴表观遗传学研究领域称之为RNA表观遗传学或表观转录组学。RNA表观遗传修饰依赖修饰酶、去修饰酶和结合蛋白三类蛋白调控发挥功能。RNA上存在上百种化学修饰,但大多数生物功能未知。
我课题组致力于开发核酸修饰化学标记测序技术,运用化学生物学、分子生物学、细胞生物学、生物信息学等技术和手段,研究核酸化学修饰和RNA表观遗传学在动植物中的生物调控功能。主要的研究方向包括:
1. 发展核酸修饰化学标记测序技术,实现核酸修饰的全转录组测序和定位;
2. 鉴定RNA修饰的修饰酶、去修饰酶和结合蛋白,阐明RNA修饰对植物生长发育、逆境响应等调控机制;
3. 改造植物RNA表观遗传修饰,实现植物高产等优质农艺性状;
4. 研究RNA表观遗传修饰在疾病中的致病分子机制;
5. 发展小分子抑制剂,调控RNA表观遗传修饰。
代表性成果
1. Qiong Yu#, Shun Liu#, Lu Yu, Yu Xiao, Shasha Zhang, Xueping Wang, Yingying Xu, Hong Yu, Yulong Li, Junbo Yang, Jun Tang, Hong-Chao Duan, Lian-Huan Wei, Haiyan Zhang, Jiangbo Wei, Qian Tang, Chunling Wang, Wutong Zhang, Ye Wang, Peizhe Song, Qiang Lu, Wei Zhang, Shunqing Dong, Baoan Song*, Chuan He*, Guifang Jia*. RNA demethylation increases the yield and biomass of rice and potato plants in the field trials. Nature Biotechnology, 2021, doi: 10.1038/s41587-021-00982-9.
2. Congyao Xu#, Zhe Wu#, Hong-Chao Duan#, Xiaofeng Fang, Guifang Jia*, Caroline Dean*. R-loop resolution promotes co-transcriptional chromatin silencing. Nature Communications, 2021, 12, 1790.
3. Peizhe Song#, Junbo Yang#, Chunling Wang, Qiang Lu, Linqing Shi, Subiding Tayier, Guifang Jia*. Arabidopsis N6-methyladenosine reader CPSF30-L recognizes FUE signal to control polyadenylation site choice in liquid-like nuclear body. Molecular Plant, 2021, 14, 571-587.
4. Ye Wang, Yu Xiao, Shunqing Dong, Qiong Yu, Guifang Jia*. Antibody-free enzyme-assisted chemical approach for detection of N6-methyladenosine. Nature Chemical Biology, 2020, 16, 896-903.
5. Xiao Zhang#, Lian-Huan Wei#, Yuxin Wang#, Yu Xiao#, Jun Liu, Wei Zhang, Ning Yan, Gubu Amu, Xinjing Tang, Liang Zhang*, Guifang Jia*. Structural insights into FTO's catalytic mechanism for the demethylation of multiple RNA substrates. Proceedings of National Academy of Sciences of the United States of America, 2019, 116, 2919.
6. Yu Xiao, Ye Wang, Qian Tang, Lianhuan Wei, Xiao Zhang, Guifang Jia*. An elongation- and ligation-based qPCR amplification method for the radiolabeling-free detection of locus-specific N6-methyladenosine modification. Angewandte Chemie International Edition, 2018, 57, 15995.
7. Lian-Huan Wei, Peizhe Song, Ye Wang, Zhike Lu, Qian Tang, Qiong Yu, Yu Xiao, Xiao Zhang, Hong-Chao Duan, Guifang Jia*. The m6A reader ECT2 controls trichome morphology by affecting mRNA stability in Arabidopsis, Plant Cell, 2018, 30, 968.
8. Hong-Chao Duan, Lian-Huan Wei, Chi Zhang, Ye Wang, Lin Chen, Zhike Lu, Peng Chen, Chuan He*, Guifang Jia*. ALKBH10B is an RNA N6-methyladenosine demethylase affecting Arabidopsis floral transition, Plant Cell, 2017, 29, 2995.
9. Yue Huang#, Jingli Yan#, Qi Li, Jiafei Li, Shouzhe Gong, Hu Zhou, Jianhua Gan, Hualiang Jiang, Guifang Jia*, Cheng Luo*, Cai-Guang Yang*. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5, Nucleic Acids Research, 2015, 43, 373.
10. Guan-Zheng Luo#, Alice MacQueen#, Guanqun Zheng#, Hongchao Duan, Louis C. Dore, Zhike Lu, Jun Liu, Kai Chen, Guifang Jia*, Joy Beigelson*, Chuan He*, Unique features of the m6A methylome in Arabidopsis thaliana, Nature Communications, 2014, 5, 5630.