表观遗传调控与干预重点实验室

　　1998 - 2002  武汉大学，获理学学士学位 (化学)

　　2002 - 2008  中国科学院生物物理研究所，获理学博士学位 (生物化学与分子生物学)

　　2009 - 2015  美国国立卫生研究院，博士后

　　2015 - 2022  清华大学生命科学学院，助理教授/副教授，博士生导师

　　2022 - 至今  中国科学院生物物理研究所，研究员，博士生导师

　　RNA在生命体发挥多种重要的生理功能，其突变或代谢失衡往往引起多种疾病。相比于蛋白质，当前RNA的高级结构研究远远滞后。mRNA技术在新冠疫苗开发方面的空前成功也激起了人们对RNA疗法的极大兴趣。

　　本课题组聚焦于RNA的整合结构生物学研究。我们一方面致力于体外与活细胞内RNA高级结构研究新方法与新方案的开发，并据此开展与人类疾病或重大生命过程密切相关的RNA的高级结构、构象动态、相互作用与功能关系的研究，另一方面致力于靶向RNA与基于RNA的新疗法的开发。课题组目前的主要研究方向为：

　　1. RNA高级结构研究新方法与新方案的开发。由于RNA固有的柔性，应用传统结构研究手段包括X射线晶体学、核磁共振和冷冻电镜对RNA进行高级结构研究非常具有挑战性，有必要开发新方法。我们将结合化学生物学与合成生物学的进展，积极开发体外与活细胞内RNA的位点特异性与区段选择性标记技术，环状RNA的制备技术，以及活细胞内RNA高级结构研究的方法。

　　2. 长链RNA高级结构与功能研究。长链RNA（包括长非编码RNA，环状RNA和真核mRNA的非翻译区等）是RNA高级结构研究的难点。基于课题组开发的RNA研究新方法与新方案，我们将整合多种方法(包括SHAPE-MaP, 小角X射线/中子散射技术、电子顺磁共振/核磁共振技术、X射线晶体学、单分子荧光共振能量转移、X射线散射干涉以及计算模拟等)，开展致病病毒 (包括黄病毒、冠状病毒) RNA、致病细菌(如结核杆菌)RNA、与神经退行性疾病密切相关真核mRNA非翻译区和lncRNA, circRNA的结构、相互作用与功能关系的研究。

　　3. RNA构象动态与功能研究。RNA的生理功能不仅与其特定的高级结构密切相关，还与RNA响应配体结合或环境变化的构象动态变化密切相关。当前，已有部分长链RNA的高分辨率结构得到解析，在此基础上，我们将结合单分子技术(包括单分子荧光共振能量转移、单分子纳米孔技术等)与系综技术(包括小角射线、电子顺磁共振、X射线散射干涉等)开展相关RNA的构象动态与功能关系研究。

　　4. 靶向RNA与基于RNA的新疗法开发。在前期结构-功能关系研究的基础上，课题组将发展RNA的稳定化技术，开发mRNA分子的理性设计和优化策略、发展靶向RNA和RNA结合蛋白的定向降解技术，为开发靶向RNA和基于RNA的生物治疗方案提供依据。

1. Keyun Huang, Xianyang Fang*. A review on recent advances in methods for site-directed spin labeling of long RNAs. International Journal of Biological Macromolecules 2023, 239:124244.

2. Xiang Chen^#, Yan Wang^#, Zhonghe Xu^#, Meng-Li Cheng, Qing-Qing Ma, Rui-Ting Li, Zheng-Jian Wang, Hui Zhao, Xiaobing Zuo, Xiao-Feng Li, Xianyang Fang*, Cheng-Feng Qin*. Zika virus RNA structure controls its unique neurotropism by bipartite binding to Musashi-1. Nature Communications 2023, 14(1): 1134

3. Lilei Xu^#, Yu Xiao^#, Jie Zhang, Xianyang Fang*. Structural insights into translation regulation by THF-II riboswitch. Nucleic Acids Research 2023, 51(2):952-965.

4. Jie Zhang, Binxian Chen, Xianyang Fang*. 3D structural analysis of long non-coding RNAs by SAXS and computational modeling. Methods in Molecular Biology 2023, 2568:147-163 (Springer Protocol Book Series).

5. Xianyang Fang*, Jose Gallego*, Yun-Xing Wang*. Deriving RNA topological structure from SAXS. Methods in Enzymology 2022, 677:479-529.

6. Yanping Hu^#, Yan Wang^#, Jaideep Singh^#，Ruirui Sun^#, Lilei Xu, Xiaolin Niu, Keyun Huang, Guangcan Bai, Guoquan Liu, Xiaobing Zuo, Chunlai Chen, Peter Z. Qin, Xianyang Fang*. Phosphorothioate-based posttranscriptional site-specific labeling of large RNAs for structural and dynamic studies. ACS Chemical Biology 2022, 17(9):2448-2460

7. Bingbing Xu^#, Changchang Cao^#, Hao Chen^#, Qiongli Jin^#, Guangnan Li^#, Junfeng Ma^#, Jieyu Zhao^#, Jianghui Zhu^#, Yiliang Ding*, Xianyang Fang*, Yongfeng Jin*, Chun Kit Kwok*, Aiming Ren*, Yue Wan*, Zhiye Wang*, Yuanchao Xue*, Huakun Zhang*, Qiangfeng Cliff Zhang*, Yu Zhou. Recent advances in RNA structurome. Science China Life Sciences 2022，65(7):1285-1324

8. Burkhard Endeward^#, Yanping Hu^#, Guangcan Bai, Guoquan Liu, Thomas F. Prisner*, Xianyang Fang*. Long-range distance determination in fully deuterated RNA with pulsed EPR spectroscopy. Biophysical Journal 2022，121(1):37-43.

9. Xiaolin Niu^#, Ruirui Sun^#, Zhifeng Chen, Yirong Yao, Xiaobing Zuo, Chunlai Chen*, Xianyang Fang*. Pseudoknot length modulates the folding, conformational dynamics and robustness of Xrn1 resistance of flaviviral xrRNAs. Nature Communications 2021, 12(1): 6417

10. Junfeng Ma, Xiang Cheng, Zhonghe Xu, Yikan Zhang, Jaione Valle, Shilong Fan, Xiaobing Zuo, Inigo Lasa, Xianyang Fang*. Structural mechanism for modulation of functional amyloid and biofilm formation by Staphylococcal Bap protein switch. The EMBO Journal 2021, 40(14): e107500. (Research Highlight on Nature Chemical Biology 2021, 17: 839)

11. Youqi Tao^#, Jingfei Xie^#, Qinglu Zhong^#, Yongyao Wang^#, Shengnan Zhang, Feng Luo, Fengcai Wen, Jingjing Xie, Jiawei Zhao, Xiaoou Sun, Houfang Long, Junfeng Ma, Qian Zhang, Jiangang Long, Xianyang Fang, Ying Lu, Dan Li, Ming Li, Jidong Zhu, Bo Sun*, Guohui Li*, Jiajie Diao*, Cong Liu*. A novel partially-open state of SHP2 points to a "multiple gear" regulation mechanism. Journal of Biological Chemistry 2021, 296: 100538.

12. Jaione Valle, Xianyang Fang, Inigo Lasa*. Revisiting Bap multidomain protein: more than sticking bacteria together. Frontiers in Microbiology 2020, 11:613581. (Review)

13. Xiaolin Niu^#, Qiuhan Liu^#, Zhonghe Xu^#, Zhifeng Chen, Linghui Xu, Lilei Xu, Jinghong Li*, Xianyang Fang*. Molecular mechanisms underlying the mechanical anisotropy of flaviviral exoribonuclease-resistant RNAs (xrRNAs). Nature Communications 2020, 11(1): 5496. (News and Views on Nature Chemical Biology 2021, 17: 933-934)

14. Yan Wang, Venkatesan Kathiresan, Yaoyi Chen, Yanping Hu, Wei Jiang, Guangcan Bai, Guoquan Liu, Peter Z. Qin*, Xianyang Fang*. Posttranscriptional site-directed spin labeling of large RNAs with an unnatural base pair system under non-denaturing conditions. Chemical Science 2020, 11: 9655-9664.

15. Yan Wang, Yaoyi Chen, Yanping Hu, Xianyang Fang*. Site-specific covalent labeling of large RNAs with nanoparticles empowered by expanded genetic alphabet transcription. Proceedings of the National Academy of Sciences 2020, 117(37): 22823-22832.

16. Yinlong Song, Yikan Zhang, Ying Pan, Jianfeng He, Yan Wang, Wei Chen, Jing Guo, Haiteng Deng, Yi Xue*, Xianyang Fang*, Xin Liang*. The dimeric organization that enhances the microtubule end-binding affinity of EB1 is susceptible to phosphorylation. Journal of Cell Science 2020, 133(9): jcs241216.

17. Qiu-Yan Zhang^#, Xiao-Feng Li^#, Xiaolin Niu, Na Li, Hong-Jiang Wang, Cheng-Lin Deng, Han-Qing Ye, Xing-Yao Huang, Qi Chen, Yan-Peng Xu, Hao-Long Dong, Xiao-Dan Li, Hui Zhao, Pei-Yong Shi, Zhi-Ming Yuan, Peng Gong, Xianyang Fang, Cheng-Feng Qin*, Bo Zhang*. Short Direct Repeats in the 3′ Untranslated Region Are Involved in Subgenomic Flaviviral RNA Production. Journal of Virology 2020，94(6): e01175-19.

18. Mengran Chen^#, Han Pan^#, Lingfei Sun^#, Peng Shi^#, Yikan Zhang, Le Li, Yuxing Huang, Jianhui Chen, Peng Jiang, Xianyang Fang, Congying Wu, and Zhucheng Chen*. Structure and regulation of human epithelial cell transforming 2 protein. Proceedings of the National Academy of Sciences 2020, 117(2)：1027-1035.

19. Yupeng Zhang^#, Yikan Zhang^#, Zhong-Yu Liu^#，Meng-Li Cheng^#, Junfeng Ma, Yan Wang, Cheng-Feng Qin*, Xianyang Fang*. Long non-coding subgenomic flavivirus RNAs have extended 3D structures and are flexible in solution. EMBO Reports 2019, 20(11): e47016.

20. Lilia Kaustov^#, Alexander Lemak^#, Hong Wu^#, Marco Faini, Lixin Fan, Xianyang Fang, Hong Zeng, Shili Duan, Abdellah Allali-Hassani, Fengling Li, Yong Wei, Masoud Vedadi, Ruedi Aebersold, Yunxing Wang, Scott Houliston, Cheryl H Arrowsmith*. The MLL1 trimeric catalytic complex is a dynamic conformational ensemble stabilized by multiple weak interactions. Nucleic Acids Research 2019, 47(17): 9433-9447.

21. Jingxia Lu^#, Jiao Li^#, Yuan Wu, Xianyang Fang, Jiapeng Zhu*, Huan Wang*. Characterization of the FMN-Dependent Cysteine Decarboxylase from Thioviridamide Biosynthesis. Organic Letters 2019, 21(12): 4676-4679.

22. Yanxiang Zhao, Yikan Zhang, Jinguang Huang, Shanshan Wang, Long Yi, Xin Zhang, Min Xu,  Xianyang Fang*, Junfeng Liu*. The effect of phosphate ion on the ssDNA binding mode of MoSub1, a Sub1/PC4 homolog from rice blast fungus. Proteins: Structure, Function, and Genetics 2019, 87(4): 257-264.

23. Yan Wang^#, Jingbo Jiang^#, Yachao Gao^#, Yang Sun, Jianfeng Dai, Yang Wu, Di Qu, Gang Ma, Xianyang Fang*. Staphylococcus epidermidis small basic protein (Sbp) forms amyloid fibrils, consistent with its function as a scaffolding protein in biofilms. Journal of Biological Chemistry 2018, 293(37): 14296-14311.

24. Senyan Zhang^#, Panpan Zhou^#, Pengfei Wang^#, Yangyang Li, Liwei Jiang, Wenxu Jia, Han Wang, Angela Fan, Dongli Wang, Xuanling Shi, Xianyang Fang, Michal Hammel,Shuying Wang, Xinquan Wang*, Linqi Zhang*. Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein. Cell Reports 2018, 24(2): 441-452.

25. Yanan Dong^#, Yajuan Mu^#, Yongchao Xie^#, Yupeng Zhang^#, Youyou Han, Yu Zhou, Wenhe Wang, Zihe Liu, Mei Wu, Hao Wang, Man Pan, Ning Xu, Cong-Qiao Xu, Maojun Yang, Shilong Fan, Haiteng Deng, Tianwei Tan, Xiaoyun Liu, Lei Liu, Jun Li, Jiawei Wang, Xianyang Fang, Yue Feng*. Structural basis of ubiquitin modification by the Legionella effector SdeA. Nature 2018, 557(7707): 674-678.

26. Yuba R. Bhandari, Lixin Fan, Xianyang Fang, George F. Zaki, Eric A. Stahlberg, Wei Jiang, Charles D. Schwieters, Jason R. Stagno, Yun-Xing Wang*. Topological Structure Determination of RNA Using Small-Angle X-Ray Scattering. Journal of Molecular Biology 2017, 429 (23): 3635-3649.

27. Xianyang Fang*, Malgorzata Michnicka, Yikan Zhang, Yun-Xing Wang, Edward P. Nikonowicz*. Capture and Release of tRNA by the T-Loop Receptor in the Function of the T-Box Riboswitch. Biochemistry 2017, 56(28): 3549-3558.

28. He Song, Xianyang Fang, Lan Jin, Gary X.Shaw, Yun-Xing Wang, Xinhua Ji*. The Functional Cycle of Rnt1p: Five Consecutive Steps of Double-Stranded RNA Processing by a Eukaryotic RNase III. Structure 2017, 25: 353-363.

29. Xian Xia^#, Xiaoyu Liu^#, Tong Li, Xianyang Fang, Zhucheng Chen*. Structure of Chromatin Remodeller Swi2/Snf2 in the Resting State. Nature Structural and Molecular Biology 2016, 23: 722-729.

30. Smita Kakar^#, Xianyang Fang^#, Lucyna Lubkowska^#, Yan Ning Zhou, Gary X. Shaw, Yun-Xing Wang,Ding Jun Jin*, Mikhail Kashlev*, Xinhua Ji*. Allosteric Activation of Bacterial Swi2/Snf2 (Switch/Sucrose Non-fermentable) Protein RapA by RNA Polymerase: BIOCHEMICAL AND STRUCTURAL STUDIES. Journal of Biological Chemistry 2015, 290 (39): 23656-69.

31. Robert A. Dick*, Siddhartha A. K. Datta*, Hirsh Nanda, Xianyang Fang, Yi Wen, Marilia Barros, Yun-Xing Wang, Alan Rein, Volker M. Vogt. Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein. Journal of Virololgy 2015, 89: 10371-10382.

32. Xianyang Fang, Jason R. Stagno, Yuba Bh.andari, Xiaobing Zuo, Yun-Xing Wang*. Small-angle X-ray scattering: a bridge between RNA secondary structures and three-dimensional topological structures. Current Opinion in Structural Biology 2015, 30: 147-160. (Review)

33. Sujay Subbayya Ithychanda, Xianyang Fang, Maradumane L. Mohan, Liang Zhu, Kalyan C. Tirupula, Sathyamangla V. Naga Prasad, Yun-Xing Wang, Sadashiva Karnik, Jun Qin*. A mechanism of global shape-dependent recognition and phosphorylation of filamin by protein kinase A. Journal of Biological Chemistry 2015, 290(13): 8527-38.

34. Yi Peng, Joseph E. Curtis, Xianyang Fang, Sarah A. Woodson*. Structural Model of the folded rpoS mRNA leader in complex with Hfq. Proceedings of the National Academy of Sciences 2014, 111(48): 17134-9.

35. Alexander Lemak, Bin Wu, Adelinda Yee, Scott Houliston, Hsiau-Wei Lee,  Aleksandras Gutmanas, Xianyang Fang, Maite Garcia, Anthony Semesi,  Yun-Xing Wang, James H. Prestegard, Cheryl H. Arrowsmith*. Structural characterization of a flexible two-domain protein in solution based using Small Angle X-ray Scattering and NMR Data. Structure 2014, 22(12): 1862-74.

36. Feng-Ming James Chang, Coyne, H. Jerome, Ramirez, Ciro Alberto Cubillas, Pablo Vinuesa Fleischmann, Xianyang Fang, Zhen Ma, Dejian Ma, John D. Helmann, Alejandro García-de los Santos, Yun-Xing Wang, Charles E. Dann III, David P. Giedroc*. Cu(I)-mediated Allosteric Switching in a Copper-sensing Operon Repressor (CsoR). Journal of Biological Chemistry 2014, 289(27): 19204-17.

37. Xianyang Fang^#, Jinbu Wang^#, Ina P. O'Carroll^#, Michelle Mitchell, Xiaobing Zuo, Yi Wang, Ping Yu, Yu Liu, Jason W. Rausch, Marzena A. Dyba, Jorgen Kjems, Charles D. Schwieters, Soenke Seifert, Randall E. Winans, Norman R. Watts, Stephen J. Stahl, Paul T. Wingfield, R. Andrew Byrd, Stuart F. J. Le Grice, Alan Rein*,Yun-Xing Wang*. An unusual topological structure of the HIV-1 rev response element. Cell 2013, 155(3): 594-605.

38. Moshe Giladi, Itay Friedberg, Xianyang Fang, Reuben Hiller, Yun-Xing Wang, Daniel Khananshvili*. G503 is obligatory for dynamic coupling of regulatory domains in NCX proteins. Biochemistry 2012, 51(37): 7313-20.

39. Moshe Giladi, Yeheskel Sasson, Xianyang Fang, Reuben Hiller, Tal Buki, Yun-Xing Wang, Joel Alan Hirsch, Daniel Khananshvili*. A common Ca²⁺-driven interdomain module governs eukaryotic NCX regulation. PLoS One 2012, 7(6): e39985.

40. George Avvakumov, John Walker, Sheng Xue, Abdellah Allali-Hassani, Abdalin Asinas, Usha Nair, Xianyang Fang, Xiaobing Zuo, Yun-Xing Wang, Keith Wilkinson, Sirano Dhe-Paganon*. Two ZnF-UBP domains in isopeptidase T (USP5). Biochemistry 2012, 51(6): 1188-98.

41. Xianyang Fang, Yingang Feng, Jinfeng Wang*. Favorable contribution of the C-terminal residue K97 to the stability of a hyperthermophilic archaeal [P62A]Ssh10b. Archives of Biochemistry and Biophysics 2009, 481(1): 52-8.

42. Xianyang Fang^#, Qiu Cui^#, Yufeng Tong, Yingang Feng, Lu Shan, Li Huang, Jinfeng Wang*. A stabilizing  α/β-hydrophobic core greatly contributes to hyperthermostability of archaeal [P62A]Ssh10b. Biochemistry 2008, 47(43): 11212-21.

43. Quan Luo^#, Xianyang Fang, Zhiwei Deng, Jinfeng Wang*. NMR study of influences of D51N mutation on backbone conformation of hyperthermophilic archaeal [P62A]Ssh10b. Chemical  Journal of Chinese Universities-Chinese 2008, 29: 546-550.

44. Yan-Jun Hu, Yi Liu*, Xue-Song Shen, Xian-Yang Fang, Song-Sheng Qu. Studies on the interaction between 1-hexylcarbamoyl-5-fluorouracil and bovine serum albumin. Journal of Molecular Structure 2005, 738: 143-147.

（资料来源：方显杨研究员，2023-05-04）