个人信息

博士生导师
研究员

Email: yzhang@cemps.ac.cn
个人网页:

研究方向

基因转录结构生物学

张余

个人简介

2000.09-2004.06 复旦大学 生命科学学院 学士
2004.09-2009.06 中国科学院上海药物研究所 博士
2009.10-2015.07 美国罗格斯大学Waksman研究所 博士后
2015.08-至今 中国科学院植物生理生态研究所,研究员/研究组长
2018年获得国家基金委“优秀青年基金”支持。相关研究成果以通讯作者发表在Science, Nature, eLife, Nature Communications, PNAS, Nucleic Acid Research, JBC等国际期刊。

研究工作

转录是RNA聚合酶(RNA Polymerase; RNAP)将遗传信息从DNA转移到RNA的过程,是遗传中心法则的关键环节。转录调控是基因差异化表达的决定性因素,决定了单细胞生物到高等动植物的几乎所有细胞层面的生命活动。因此,解析 RNAP的三维结构、工作机制与调控方式一直以来都是生命科学的前沿领域。细菌基因组由1个RNAP执行转录,真核生物的细胞核由5个RNAP执行转录(Polymerase I, II, III, IV, V;其中Pol IV, V为植物特有),线粒体基因组由1个噬菌体来源的RNAP执行转录,叶绿体基因组由1个噬菌体来源的RNAP和1个细菌来源的RNAP同时执行转录。

本研究组以噬菌体、细菌、酵母和植物的细胞核与细胞器RNAP为研究对象,探索了转录在基因表达、DNA修复、DNA甲基化过程中的重要功能和工作机制。主要的研究方向包括但不限于:
1. 细菌转录机制和调控机理
2. 细菌转录与DNA修复关联的分子机制
3. 噬菌体和细菌免疫
4. 植物Pol IV和Pol V介导基因组甲基化的工作机制
5. 植物叶绿体的基因转录和调控机制
6. 细菌和植物代谢途径关键酶的结构和催化机制解析

主要成果

    1. Dong-Lei Yang*, Kun Huang, Deyin Deng, Yuan Zeng, Zhenxing Wang*, and Yu Zhang*. DNA-dependent RNA polymerases in plants. The Plant Cell (2023): koad195.

    2. Hong-Wei Zhang#, Kun Huang#, Zhan-Xi Gu#, Xiao-Xian Wu, Jia-Wei Wang, and Yu Zhang*. A cryo-EM structure of KTF1-bound polymerase V transcription elongation complex. Nature Communications 14, no. 1 (2023): 3118.

    3. Liqiang Shen#, Giorgio Lai#, Linlin You#, Jing Shi, Xiaoxian Wu, Maria Puiu, Zhanxi Gu, Yu Feng*, Yulia Yuzenkova*, and Yu Zhang*. An SI3-σ arch stabilizes cyanobacteria transcription initiation complex. Proceedings of the National Academy of Sciences 120, no. 16 (2023): e2219290120.

    4. Xiaoxian Wu#, Chengzhi Yu#, Wenhui Mu, Zhanxi Gu, Yu Feng, Yu Zhang*, The structural mechanism for transcription activation by Caulobacter crescentus GcrA, Nucleic Acids Research 2023; doi: 10.1093/nar/gkad01

    5. Linlin You, Expery O.Omollo, Chengzhi Yu, Rachel A Mooney, Jing Shi, Liqiang Shen, Xiaoxian Wu, Aijia Wen, Dingwei He, Yuan Zeng, Yu Feng*, Robert Landick*, Yu Zhang*, Nature 2023; 613(7945):783-789

    6. Dingwei He#, Linlin You#, Xiaoxian Wu, Jing Shi, Aijia Wen, Zhi Yan, Wenhui Mu, Chengli Fang, Yu Feng*, Yu Zhang*. Pseudomonas aeruginosa SutA wedges RNAP lobe domain open to facilitate promoter DNA unwinding. Nature communications 2022, 13(1), 4204.

    7. Binod K. Bharati#, Manjunath Gowder#, Fangfang Zheng, Khaled Alzoubi,Vladimir Svetlov, Venu Kamarthapu, Jacob W. Weaver, Vitaly Epshtein, Nikita Vasilyev, Liqiang Shen, Yu Zhang*, Evgeny Nudler*. Crucial role and mechanism of transcription-coupled DNA repair in bacteria. Nature 2022; 604, 152-159.

    8. Yu Liu, Libing Yu, Chirangini Pukhrambam, Jared T. Winkelman, Emre Firlar, Jason T. Kaelber, Yu Zhang, Bryce E. Nickels, and Richard H. Ebright*. Structural and mechanistic basis of reiterative transcription initiation. Proceedings of the National Academy of Sciences 2022, 119, no. 5: e2115746119.

    9. Chengli Fang, and Yu Zhang*. Bacterial MerR family transcription regulators: activationby distortion. Acta Biochimica et Biophysica Sinica 2022, 54 (1): 1-12.

    10. Kun Huang#, Xiao-Xian Wu#, Cheng-Li Fang#, Zhou-Geng Xu#, Hong-Wei Zhang, Jian Gao, Chuan-Miao Zhou, Lin-Lin You, Zhan-Xi Gu, Wen-Hui Mu, Yu Feng*, Jia-Wei Wang*, Yu Zhang*. Pol IV and RDR2: A two-RNA-polymerase machine that produces double-stranded RNA. Science 2021;374(6575):1579-1586.

    11. Hao Zhang, Nuo Cheng, Zhihui Li, Ling Bai, Chengli Fang, Yuwen Li, Weina Zhang, Xue Dong, Minghao Jiang, Yang Liang, Sujiang Zhang, Jianqing Mi, Jiang Zhu, Yu Zhang, Sai-Juan Chen, Yajie Zhao, Xiang-Qin Weng, Weiguo Hu*, Zhu Chen*, Jinyan Huang*, Guoyu Meng*. DNA crosslinking and recombination‐activating genes 1/2 (RAG1/2) are required for oncogenic splicing in acute lymphoblastic leukemia. Cancer Communications 2021. 41, no. 11: 1116-1136

    12. Chengli Fang#, Steven J. Philips#, Xiaoxian Wu, Kui Chen, Jing Shi, Liqiang Shen, Juncao Xu, Yu Feng*, Thomas V. O’Halloran*, and Yu Zhang*. CueR activates transcription through a DNA distortion mechanism. Nature Chemical Biology 2021,17: 57-64.

    13. Wenyue Dong, Xiaoqun Nie, Hong Zhu, Qingyun Liu, Kunxiong Shi, Linlin You, Yu Zhang, Hongyan Fan,Bo Yand, Chen Niu*, Liang-Dong Lyu*, Guo-Ping Zhao, Chen Yang*. Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence. Proceedings of the National Academy of Sciences 2021, no. 16: e2019305118

    14. Kyle S. Skalenko, Lingting Li, Yuanchao Zhang, Irina O. Vvedenskaya, Jared T. Winkelman, Alexander L. Cope, Deanne M. Taylor, Premal Shaha, Richard H. Ebright, Justin B. Kinneyg, Yu Zhang, and Bryce E. Nickels*. Promoter-sequence determinants and structural basis of primer-dependent transcription initiation in Escherichia coli. Proceedings of the National Academy of Sciences 2021,118, no. 27: e2106388118

    15. Chengli Fang#, Linyu Li#, Yihan Zhao, Xiaoxian Wu, Steven J. Philips, Linlin You, Mingkang Zhong, Xiaojin Shi, Thomas V. O'Halloran, Qunyi Li, Yu Zhang*. The bacterial multidrug resistance regulator BmrR distorts promoter DNA to activate transcription. Nature communications 2020, 11: 1-9.

    16. Weifeng Huang, Yang Zhang, Liqiang Shen, Qian Fang, Qun Liu, Chenbo Gong, Chen Zhang, Yong Zhou, Cui Mao, Yongli Zhu, Jinghong Zhang, Hongping Chen, Yu Zhang, Yongjun Lin, Ralph Bock and Fei Zhou*. Accumulation of the RNA polymerase subunit RpoB depends on RNA editing by OsPPR16 and affects chloroplast development during early leaf development in rice." New Phytologist 2020, 228, no. 4: 1401-1416.

    17. Lingting Li#, Vadim Molodstov#, Wei Lin, Richard Ebright*, Yu Zhang*. RNA extension drives a stepwise displacement of an initiation-factor structural module in initial transcription. PNAS 2020, 117(11): 5801-5809.

    18. Ningning Zhuang#, Hao Zhang#, Lingting Li, Xiaoxian Wu, Chen Yang*, and Yu Zhang*. Crystal structures and biochemical analyses of the bacterial arginine dihydrolase ArgZ suggests a “bond rotation” catalytic mechanism. Journal of Biological Chemistry 2020, 295, 7: 2113-2124.

    19. Fulin Wang#, Jing Shi#, Dingwei He#, Bei Tong, Chao Zhang, Aijia Wen, Yu Zhang*, Yu Feng*, and Wei Lin*. Structural basis for transcription inhibition by E. coli SspA. Nucleic acids research 2020, 48: 9931-9942.

    20. JianPing Huang#, Chengli Fang#, Xiaoyan Ma#, Li Wang, Jing Yang, Jianying Luo, Yijun Yan, Yu Zhang*, Sheng-Xiong Huang*. Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation. Nature communications 2019, 10(1): 4036.

    21. Juncao Xu#, Kaijie Cui#, Liqiang Shen, Jing Shi, Lingting Li, Linlin You, Chengli Fang, Guoping Zhao*, Yu Feng*, Bei Yang*, Yu Zhang*. Crl activates transcription by stabilizing active conformation of the master stress transcription initiation factor. eLife 2019, 8, e50928.

    22. Jing Shi#, Aijia Wen#, Minxing Zhao#, Linlin You, Yu Zhang, Yu Feng*, Structural basis of σ appropriation. Nucleic Acid Research 2019, 47(17):9423-9432.

    23. Jing Shi, Xiang Gao, Tongguan Tian, Zhaoyang Yu, Bo Gao, Aijia Wen, Linlin You, Shenghai Chang, Xing Zhang, Yu Zhang, Yu Feng*, Structural basis of Q-dependent transcription antitermination, Nature Communications 2019, 10(1): 2925

    24. Linlin You, Jing Shi, Liqiang Shen, Lingting Li, Chengli Fang, Chengzhi Yu, Wenbo Cheng, Yu Feng*, Yu Zhang*. Structural basis for transcription antitermination at bacterial intrinsic terminator. Nature communications 2019. 10(1) :3048

    25. Chengli Fang#, Lingting Li#, Liqiang Shen, Jing Shi, Sheng Wang*, Yu Feng*, Yu Zhang*. Structures and mechanism of transcription initiation by bacterial ECF factors. Nucleic Acids Research 2019, 47(13):7094-7104

    26. Lingting Li#, Chengli Fang#, Ningning Zhuang, Tiantian Wang, Yu Zhang*. Structural basis for transcription initiation by bacterial ECF σ factors. Nature Communications 2019. 10(1) :1153

    27. Irina O. Vvedenskaya#, Jeremy G. Bird#, Yuanchao Zhang#, Yu Zhang, Xinfu Jiao, Ivan Barvík, Libor Krásny, Megerditch Kiledjian, Deanne M.Taylor, Richard H. Ebright*, Bryce E.Nickels*. CapZyme-Seq Comprehensively Defines Promoter-Sequence Determinants for RNA 5′ Capping with NAD+. Molecular Cell 2018. 70(3): 553-564

    28. Xiaoxian Wu#, Diane L. Haakonsen#, Allen G. Sanderlin, Yue J, Liu, Liqiang Shen, Ningning Zhuang, Michael T. Laub*, Yu Zhang*. Structural insights into the unique mechanism of transcription activation by Caulobacter crescentus GcrA. Nucleic Acids Research 2018. 46 (6): 3245-3256.

    29. Xiaobiao Han#, Liqiang Shen#, Qijun Wang, Xufeng Cen, Jin Wang, Meng Wu, Peng Li, Wei Zhao*, Yu Zhang*, and Guoping Zhao*. Cyclic AMP inhibits the activity and promotes the acetylation of acetyl-CoA synthetase through competitive binding to the ATP/AMP pocket. Journal of Biological Chemistry 2017 292: 1374-1384.

    30. Sonia I. Maffioli#, Yu Zhang#, David Degen#, Thomas Carzaniga, Giancarlo Del Gatto, Stefania Serina, Paolo Monciardini, Carlo Mazzetti, Paola Guglierame, Gianpaolo Candiani, Alina Iulia Chiriac, Giuseppe Facchetti, Petra Kaltofen, Hans-Georg Sahl, Gianni Dehò, Stefano Donadio*, and Richard H. Ebright*. Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase: pseudouridimycin. Cell 2017, 15;169(7):1240-1248.e23

    31. Jeremy G. Bird#, Yu Zhang#, Yuan Tian, Natalya Panova, Ivan Barvík, Landon Greene, Min Liu, Brian Buckley, Libor Krásny, Jeehiun K. Lee, Craig D. Kaplan, Richard H. Ebright*, Bryce E. Nickels*. The mechanism of RNA 5' capping with NAD+, NADH, and desphospho-CoA. Nature 2016, 535(7612): 444-447.

    32. Jared T Winkelman#, Irina O Vvedenskaya#, Yuanchao Zhang#, Yu Zhang#, Jeremy G Bird, Deanne M Taylor, Richard L Gourse, Richard H Ebright*, Bryce E Nickels*. Multiplexed protein-DNA cross-linking: Scrunching in transcription start site selection. Science 2016, 351(6277):1090-1093

    33. Yu Zhang#, David Degen#, Mary X Ho#, Elena Sineva, Katherine Y Ebright, Yon W Ebright, Vladimir Mekler, Hanif Vahedian-Movahed, Yu Feng, Ruiheng Yin, Steve Tuske, Herbert Irschik, Rolf Jansen, Sonia Maffioli, Stefano Donadio, Eddy Arnold, Richard H Ebright*. GE23077 binds to the RNA polymerase “I” and “I+1” sites and prevents the binding of initiating nucleotides. Elife 2014, 3, e02450

    34. Yu Zhang, Yu Feng, Sujoy Chatterjee, Steve Tuske, Mary X Ho, Eddy Arnold, Richard H Ebright*. Structural basis of transcription initiation. Science 2012, 338 (6110), 1076-1080

    35. Yu Zhang#, Haitao Zhang#, Xin-gang Yao#, Hong Shen, Jing Chen, Chenjing Li, Lili Chen, Mingyue Zheng, Jiming Ye, Lihong Hu*, Xu Shen*, Hualiang Jiang*. (+)-Rutamarin as a dual inducer of both GLUT4 translocation and expression efficiently ameliorates glucose homeostasis in insulin-resistant mice. PLOS ONE 2012, 7 (2), e31811

    36. Yu Zhang#, Yan Li#, Yue-wei Guo*, Hua-liang Jiang, Xu Shen*. A sesquiterpene quinone, dysidine, from the sponge Dysidea villosa, activates the insulin pathway through inhibition of PTPases. Acta Pharmacol Sin. 2009, 30 (3), 333-345

    37. Qiong Liu#, Yu Zhang#, Zhonghui Lin, Hong Shen, Lili Chen, Lihong Hu*, Hualiang Jiang*, Xu Shen*. Danshen extract 15,16-dihydrotanshinone I functions as a potential modulator against metabolic syndrome through multi-target pathways. J Steroid Biochem Mol Biol. 2010, 120 (4), 155-163.

    38. Deju Ye#, Yu Zhang#, Mingfang Zheng, Xu Zhang, Xiaomin Luo, Xu Shen*, Hualiang Jiang*, Hong Liu*. Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity. Bioorg Med Chem 2010, 18 (5), 1773-1782

    39. Tiancen Hu#, Yu Zhang#, Lianwei Li, Shuai Chen, Jing Chen, Jianping Ding, Hualiang Jiang*, Xu Shen*. Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure. Virology 2009, 388 (2), 324-334