杰出青年科学基金获得者

　　1995             浙江大学生物系，学士

　　2000             金沙集团1862cc，博士

　　2001 - 2005  美国纽约纪念斯隆凯特琳癌症研究所，Dinshaw Patel实验室，博士后

　　2005 - 2011  北京生命科学研究所，研究员

　　2011 - 2014  北京生命科学研究所，高级研究员

　　2014 - 至今  金沙集团1862cc生物物理所，研究员

　　RNA分子在蛋白质翻译、RNA修饰和加工、基因调控等多种过程中发挥着重要的作用。我们实验室的主要兴趣集中在和RNA生物学相关的结构研究，包括真核生物核糖体的组装、RNA修饰和RNA沉默等领域，主要使用X射线晶体学、电镜、核磁共振、生化、酵母遗传操作等技术手段。

　　1. 真核生物核糖体组装

　　蛋白质工厂——核糖体是由RNA和蛋白质组成的超级复合物，它在体内的组装需要经历高度复杂的过程。在出芽酵母Saccharomyces cerevisiae中，有200多个保守的蛋白质组装因子和大量非编码RNA参与核糖体的组装。我们以出芽酵母为模式生物，研究核糖体体内组装的分子过程、组装因子的结构和功能以及核糖体前体的结构。

　　2. H/ACA和C/D RNA蛋白质复合物

　　H/ACA 和 C/D RNA是两大类古老的非编码RNA，它们和蛋白质结合形成多元复合物，主要在RNA的假尿嘧啶合成和2'-O甲基化修饰中，发挥结合特异底物的向导作用。我们研究H/ACA和C/D 两类RNA蛋白质复合物的空间结构、生化机制和生物发生过程。

　　3. RNA沉默

　　多种小RNA(siRNA, miRNA, crRNA)作为特异性决定因子在真核和原核生物中控制着基因的沉默。我们研究这些小RNA的加工、调控机制和效应复合物。

1. Jianxiu Zhang, Ying-Ying Wang, Li-Lin Du and Keqiong Ye*. Cryo-EM structure of fission yeast tetrameric α-mannosidase Ams1. FEBS Open Bio. 2020 Sep 27. doi: 10.1002/2211-5463.12988

2. Yifei Du^#, Weidong An^#, Xing Zhu, Qi Sun, Jia Qi, Keqiong Ye*. Cryo-EM structure of 90S small ribosomal subunit precursors in transition states. Science 2020 Sep 18; 369(6510), 1477-1481.

3. Zuxiao Yang^#, Jiayin Wang^#, Lin Huang, David MJ Lilley, Keqiong Ye*. Functional organization of box C/D RNA-guided RNA methyltransferase. Nucleic Acids Res. 2020 May 21; 48, 5094-5105.

4. Jing Chen, Liman Zhang, Keqiong Ye*. Functional regions in the 5' external transcribed spacer of yeast pre-rRNA. RNA. 2020 Jul; 26(7), 866-877. Epub 2020 Mar 25,

5. Jones AX, Cao Y, Tang YL, Wang JH, Ding YH, Tan H, Chen ZL, Fang RQ, Yin J, Chen RC, Zhu X, She Y, Huang N, Shao F, Ye K, Sun RX, He SM, Lei X, Dong MQ. Improving mass spectrometry analysis of protein structures with arginine-selective chemical cross-linkers. Nat Commun. 2019 Sep 2; 10(1):3911.

6. Ren X, Hu B, Song M, Ding Z, Dang Y, Liu Z, Zhang W, Ji Q, Ren R, Ding J, Chan P, Jiang C, Ye K, Qu J, Tang F, Liu GH. Maintenance of Nucleolar Homeostasis by CBX4 Alleviates Senescence and Osteoarthritis. Cell Rep. 2019 Mar 26; 26(13):3643-3656.

7. Weidong An, Yifei Du, Keqiong Ye*. Structural and functional analysis of Utp24, an endonuclease for processing 18S ribosomal RNA. PLoS One 2018 Apr 11; 13(4):e0195723.

8. Dejian Zhou^#, Xing Zhu^#, Sanduo Zheng, Dan Tan, Meng-Qiu Dong, Keqiong Ye*. Cryo-EM structure of an early precursor of large ribosomal subunit reveals a half-assembled intermediate. Protein Cell. 2019 Feb; 10(2):120-130. Epub 2018 Mar 19

9. Shu S, Ye K* (2018) Structural and functional analysis of ribosome assembly factor Efg1. Nucleic Acids Res. doi: 10.1093/nar/gky011

10. Hu J, Zhu X, Ye K*. (2017) Structure and RNA recognition of ribosome assembly factor Utp30. RNA. 12:1936-1945

11. Li D, He W, Liu X, Zheng S, Qi Y, Li H, Mao F, Liu J, Sun Y, Pan L, Du K, Ye K, Li W*, Sui J*. (2017) A potent human neutralizing antibody Fc-dependently reduces established HBV infections. Elife. pii: e26738. doi: 10.7554/eLife.26738.

12. Chen W, Xie Z, Yang F, Ye K*. (2017) Stepwise assembly of the earliest precursors of large ribosomal subunits in yeast. Nucleic Acids Res. 45(11):6837-6847.

13. Sun Q^#, Zhu X^#, Qi J^#, An W^#, Lan P, Tan D, Chen R, Wang B, Zheng S, Zhang C, Chen X, Zhang W, Chen J, Dong MQ, Ye K*. (2017) Molecular architecture of the 90S small subunit pre-ribosome. Elife. pii: e22086, doi: 10.7554/eLife.22086.

14. Bing Wang, Keqiong Ye*. (2017) Nop9 binds the central pseudoknot region of 18S rRNA. Nucleic Acids Res. 45(6):3559-3567.

15. Shen M^#, Zhang N^#, Zheng S^#, Zhang WB, Zhang HM, Lu Z, Su QP, Sun Y, Ye K, Li XD*. (2016) Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor. Proc Natl Acad Sci U S A. 113(40):E5812-E5820.

16. Zuxiao Yang, Jinzhong Lin, and Keqiong Ye* (2016) Box C/D guide RNAs recognize a maximum of 10 nt of substrates. Proc Natl Acad Sci U S A. 113(39):10878-83.

17. Cheng Zhang, Qi Sun, Rongchang Chen, Xining Chen, Jinzhong Lin and Keqiong Ye* (2016) Integrative structural analysis of the UTPB complex, an early assembly factor for eukaryotic small ribosomal subunits. Nucleic Acids Res. doi: 10.1093/nar/gkw562

18. Ding YH, Fan SB, Li S, Feng BY, Gao N, Ye K, He SM, Dong MQ*. (2016)　Increasing the Depth of Mass-Spectrometry-Based Structural Analysis of Protein Complexes through the Use of Multiple Cross-Linkers. Anal Chem. 88(8):4461-9.

19. Liman Zhang^#, Chen Wu^#, Gaihong Cai, She Chen, Keqiong Ye* (2016) Stepwise and dynamic assembly of the earliest precursors of small ribosomal subunits in yeast. Genes & Dev. 30:718-32

20. Tan D, Li Q, Zhang MJ, Liu C, Ma C, Zhang P, Ding YH, Fan SB, Tao L, Yang B, Li X, Ma S, Liu J, Feng B, Liu X, Wang HW, He SM, Gao N, Ye K, Dong MQ*, Lei X*. (2016)　Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states. Elife. 5. pii: e12509.

21. Shukun Luo^#, Xiaoran Xin^#, Li-Lin Du*, Keqiong Ye*, Yi Wei (2015) Dimerization mediated by a divergent FHA domain is essential for the DNA damage and spindle functions of fission yeast Mdb1. J. Biol. Chem. 290:21054-66

22. Xing Zhu and Keqiong Ye* (2015) Cmr4 is the slicer in the RNA-targeting Cmr CRISPR complex. Nucleic Acids Res. 43(2):1257-67

23. Sanduo Zheng, Raffaella Villa, Jia Wang, Yingang Feng, Jinfeng Wang, Peter B. Becker and Keqiong Ye* (2014) Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation. Genes & Dev. 28: 2652-2662

24. Sanduo Zheng^#, Pengfei Lan^#, Ximing Liu and Keqiong Ye* (2014) Interaction of ribosome assembly factors Krr1 and Faf1 is essential for formation of small ribosomal subunit in yeast. J. Biol. Chem. 289:22692-22703.

25. Sanduo Zheng and Keqiong Ye* (2014) Purification, crystallization and preliminary X-ray diffraction  analysis of Imp3 in complex with an Mpp10 peptide involved in yeast ribosome biogenesis. Acta Cryst. F90, 918-921

26. Dejian Zhou, Keqiong Ye* (2014) CLIP techniques in studying protein-RNA interactions. Chinese Bulletin of Life Sciences 26(3) 207-212 (review in Chinese)

27. Cheng Zhang, Jinzhong Lin, Weixiao Liu, Xining Chen, Rongchang Chen and Keqiong Ye* (2014) Structure of Utp21 tandem WD domain provides insight into the organization of the UTPB complex involved in ribosome synthesis. PLoS ONE 9(1): e86540.

28. Jing Lu, Mengyi Sun and Keqiong Ye* (2013) Structural and functional analysis of Utp23, a yeast ribosome synthesis factor with degenerate PIN domain. RNA. 19:1815-24.

29. Jinzhong Lin^#, Jing Lu^#, Yingang Feng, Mengyi Sun and Keqiong Ye* (2013) An RNA-binding complex involved in ribosome biogenesis contains a protein with homology to tRNA CCA-adding enzyme. PLoS Biol 11(10): e1001669.

30. Jie Zheng, Lei Zhang, Junbin Zhang, Xiaoxia Wang, Keqiong Ye, Zhen Xi*, Quan Du*, Zicai Liang* (2013) Single modification at position 14 of siRNA strand abolishes its gene-silencing activity by decreasing both RISC loading and target degradation. FASEB J. 10:4017-26.

31. Yue-He Ding^#, Yun-Guang Du^#, Shukun Luo^#, Yu-Xin Li, Tie-Mei Li, Sawako Yoshina, Xing Wang, Karsten Klage, Shohei Mitani, Keqiong Ye*, Meng-Qiu Dong* (2013)Characterization of PUD-1 and PUD-2, Two Proteins Up-Regulated in a Long-Lived daf-2 Mutant. PLoS ONE 8(6):e67158.

32. Liman Zhang, Jinzhong Lin and Keqiong Ye* (2013) Structural and functional analysis of the U3 snoRNA binding protein Rrp9. RNA 19:701-711.

33. Sanduo Zheng^#, Jia Wang^#, Yingang Feng^#,*, Jinfeng Wang and Keqiong Ye* (2012) Solution structure of MSL2 CXC domain reveals an unusual Zn3Cys9 cluster and similarity to pre-SET domains of histone lysine methyltransferases. PLoS ONE, 7(9):e45437.

34. Xinxing Yang, Jinqi Duan, Shuang Li, Peng Wang, Shoucai Ma, Keqiong Ye* and Xin Sheng Zhao* (2012) Kinetic and thermodynamic characterization of the reaction pathway of box H/ACA RNA-guided pseudouridine formation. Nucleic Acids Res.40:10925-36.

35. Bing Yang^#, Yan-Jie Wu^#, Ming Zhu^#, Sheng-Bo Fan, Jinzhong Lin, Kun Zhang, Shuang Li, Hao Chi, Yu-Xin Li, Hai-Feng Chen, Shu-Kun Luo, Yue-He Ding, Le-Heng Wang, Zhiqi Hao, Li-Yun Xiu, She Chen, Keqiong Ye, Si-Min He* and Meng-Qiu Dong* (2012) Identification of cross-linked peptides from complex samples. Nature Method. 9:904-906.

36. Xing Zhu and Keqiong Ye* (2012) Crystal structure of Cmr2 suggests a nucleotide cyclase-related enzyme in type III CRISPR-Cas systems. FEBS Letters 586:939-945.

37. Wei Zhang, Yang Zhao, Yan Guo and Keqiong Ye* (2012) Plant actin-binding protein SCAB1 is dimeric actin cross-linker with atypical pleckstrin homology domain. J. Biol. Chem. 287: 11981-11990.

38. Shukun Luo and Keqiong Ye* (2012) Dimerization, but not phosphothreonine binding, is conserved between the forkhead-associated domains of Drosophila MU2 and human MDC1. FEBS Letters. 586:344-349.

39. Jinping Liu^#, Shukun Luo^#, Hongchang Zhao, Ji Liao, Jing Li, Chunying Yang, Bo Xu, David F. Stern, Xingzhi Xu* and Keqiong Ye* (2012) Structural mechanism of the phosphorylation-dependent dimerization of the MDC1 forkhead-associated domain. Nucleic Acids Res. 40:3898-912.

40. Shuang Li^#, Jingqi Duan^#, Dandan Li, Shoucai Ma and Keqiong Ye* (2011) Structure of the Shq1-Cbf5-Nop10-Gar1 complex and implications for H/ACA RNP biogenesis and dyskeratosis congenita. EMBO J. 30:5010-5020.

41. Shuang Li, Jingqi Duan, Dandan Li, Bing Yang, Mengqiu Dong and Keqiong Ye* (2011) Reconstitution and structural analysis of the yeast box H/ACA RNA-guided pseudouridine synthase. Genes Dev 25:2409-2421.

42. Jinzhong Lin^#, Liman Zhang^#, Shaomei Lai, Keqiong Ye* (2011) Structure and molecular evolution of CDGSH iron-sulfur domains. PLoS ONE, 6(9): e24790.

43. Yang Zhao, Shuangshuang Zhao, Tonglin Mao, Xiaolu Qu, Wanhong Cao, Li Zhang, Wei Zhang, Liu He, Sidi Li, Sulin Ren, Jinfeng Zhao, Guoli Zhu, Shanjin Huang, Keqiong Ye, Ming Yuan, and Yan Guo. (2011) The Plant-Specific Actin Binding Protein SCAB1 Stabilizes Actin Filaments and Regulates Stomatal Movement in Arabidopsis. Plant Cell. 23:2314-2330.

44. Bihong Guo, Jinzhong Lin and Keqiong Ye* (2011) Structure of the autocatalytic cysteine protease domain of potyvirus helper-component proteinase. J. Biol. Chem. 286: 21937-21943.

45. Jinzhong Lin, Shaomei Lai, Ru Jia, Anbi Xu, Liman Zhang, Jing Lu and Keqiong Ye* (2011) Structural basis of site-specific ribose methylation by box C/D RNA protein complexes. Nature 469: 559-563.

46. Wei Zhang and Keqiong Ye* (2010) Progress in structural biology of RNA silencing. Chinese Bulletin of Life Sciences 22: 608-615. (review in Chinese)

47. Lin Huang, Ping Yin, Xing Zhu, Yi Zhang and Keqiong Ye* (2010) Crystal structure and centromere binding of the plasmid segregation protein ParB from pCXC100. Nucleic Acids Res. 39: 2954-2968.

48. Mei Shen, Yi Xu, Ru Jia, Xueping Zhou and Keqiong Ye* (2010) Size-independent and non-cooperative recognition of dsRNA by the Rice stripe virus RNA silencing suppressor NS3. J Mol Biol. 404: 665-679.

49. Keqiong Ye*, Ru Jia, Jinzhong Lin, Minghua Ju, Jin Peng, Anbi Xu and Liman Zhang (2009) Structural organization of box C/D RNA-guided RNA methyltransferase. Proc Natl Acad Sci USA, 106: 13808-13813.

50. Jingqi Duan, Ling Li, Jing Lu, Wei Wang and Keqiong Ye* (2009) Structural mechanism of substrate RNA recruitment in H/ACA RNA-guided pseudouridine synthase. Mol Cell 34:427-439.

51. Keqiong Ye*. (2007) H/ACA RNAs, proteins and complexes. Curr. Opin. Struct. Biol. 17:287-292. (review)

52. Jinzhong Lin, Tao Zhou, Keqiong Ye* and Jinfeng Wang* (2007) Crystal structure of human mitoNEET reveals distinct groups of iron-sulfur proteins. Proc Natl Acad Sci USA 104:14640-14645.

53. Ling Li and Keqiong Ye* (2006) Crystal structure of an H/ACA box ribonucleoprotein particle. Nature 443: 302-307.

54. Patel, D.J., Ma, J.-B., Yuan, Y.-R.,  Ye, K., Pei, Y., Kuryavyi, V.,  Malinina, L., Meister, G. and  Tuschl, T. (2006) Structural Biology of RNA Silencing and Its Functional Implications. Cold Spring Harb Symp. Quant Biol. 71:81-93. (review)

55. Ye, K. and Patel, D.J. (2005) RNA silencing suppressor p21 of Beet Yellows Virus forms an RNA-binding octameric ring structure. Structure 13:1375-1384.

56. Ma, J.^#, Ye, K^#. and Patel, D.J. (2004) Structural mechanism of overhang-specific small interfering RNA recognition of the PAZ domain. Nature 429:318-322.

57. Ye, K., Malinina, L. and Patel, D.J. (2003) Recognition of small interfering RNA by a viral suppressor of RNA silencing. Nature 426:874-878.

58. Yao, Y, Wu, Y, Qian, C, Ye, K, Wang, J, Tang, W. (2003) NMR study of the conformational transition of cytochrome c upon the displacement of Met80 by exogenous ligand: structural and magnetic characterization of azidoferricytochrome c. Biophys Chem. 103:13-23.

59. Ye, K., Serganov, A., Hu, W., Garber, M. and Patel, D.J. (2002) Ribosome-associated factor Y adopts a fold resembling a double-stranded RNA binding domain scaffold. Eur. J. Biochem. 269:5182-5191.

60. Yao, Y., Qian, C., Ye, K., Wang, J., Bai, Z. and Tang, W. (2002) Solution structure of cyanoferricytochrome c: ligand-controlled conformational flexibility and electronic structure of the heme moiety. J. Biol. Inorg. Chem. 7:539-547.

61. Qian, C., Yao, Y., Ye, K., Wang, J., Tang, W., Wang, Y., Wang, W., Lu, J., Xie Y. and Huang, Z. (2001) Effects of charged amino-acid mutation on the solution structure of cytochrome b(5) and binding between cytochrome b(5) and  cytochrome c. Protein Sci. 10:2451-2459.

62. Ye, K. and Wang, J. (2001) Self-association reaction of denatured staphylococcal nuclease fragments characterized by heteronuclear NMR. J. Mol. Biol. 307:309-322.

63. Ye, K., Jing, G. and Wang, J. (2000) Interactions between subdomains in the partially folded state of staphylococcal nuclease.  Biochim.  Biophys.  Acta.  1479:123-134.

（资料来源：叶克穷研究员，2020-10-28）