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Keqiong Ye

Ph.D, Prof.

Principle Investigator Chinese Academy of Sciences Key Laboratory of Nucleic Acid Biology, IBP

Research Interests: Structural Biology of RNA


Email: yekeqiong@ibp.ac.cn

Tel: 010-64887672


Address: 15 Datun Road, Chaoyang District, Beijing, 100101, China


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Biography

1995 B.S. Biological Science and Technology, Zhejiang University, Hangzhou, China

2000 Ph.D. Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

2001 - 2005 Postdoctoral research with Dr. Dinshaw J. Patel. Memorial Sloan-Kettering Cancer Center, New York, USA

2005 - 2011 Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2011 - 2014 Associate Investigator, National Institute of Biological Sciences, Beijing, China

2014 - Investigator, Institute of Biophysics, Chinese Academy of Sciences

Awards
Membership in Academies & Societies
Research Interests

The RNA molecule plays important roles in diverse biological processes, such as protein synthesis, RNA processing and modification, and gene regulation. Our laboratory is interested in structural studies related to RNA biology, focusing on eukaryotic ribosome assembly, RNA modification and RNA silencing. We use X-ray crystallography, electron microscopy, NMR, biochemistry and yeast genetics in our research.

1. Ribosome assembly in eukaryotes

The ribosome, the factory of protein, is a large RNA-protein complex that is assembled through a highly complex processin cells. In the budding yeast Saccharomyces cerevisiae, more than 200 conserved protein assembly factors and many non-coding RNAs are involved in ribosome assembly. We use the budding yeast as model organism and study the molecular events of ribosome assembly, the structure and function of assembly factors and the structure of pre-ribosomes.

2. H/ACA and C/D RNA-protein complex

The H/ACA and C/D RNA are two classes of ancient non-coding RNAs and mainly function as guide in multicomponent RNA-protein complexes during pseudouridylation and 2'-O-methylation of RNA. We study the structure, biochemical mechanism and biogenesis of the H/ACA and C/D RNA-protein complexes.

3. RNA silencing

Several types of small RNAs (siRNA, miRNA, crRNA) serve as the specificity determinant in gene silencing in eukaryotes and prokaryotes. We study the processing and regulation of these small RNAs and their effector complexes.

Grants
Selected Publications

1. Jianxiu Zhang, Ying-Ying Wang, Li-Lin Du andKeqiong 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.Science2020 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 One2018 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, andKeqiong 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 andKeqiong 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 andKeqiong 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 andKeqiong 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 andKeqiong 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 andKeqiong 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 Sciences26(3) 207-212 (review in Chinese)

27. Cheng Zhang, Jinzhong Lin, Weixiao Liu, Xining Chen, Rongchang Chen andKeqiong Ye*(2014) Structure of Utp21 tandem WD domain provides insight into the organization of the UTPB complex involved in ribosome synthesis.PLoS ONE9(1): e86540.

28. Jing Lu, Mengyi Sun andKeqiong 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 andKeqiong Ye*(2013) An RNA-binding complex involved in ribosome biogenesis contains a protein with homology to tRNA CCA-adding enzyme.PLoS Biol11(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 ONE8(6):e67158.

32. Liman Zhang, Jinzhong Lin andKeqiong Ye*(2013) Structural and functional analysis of the U3 snoRNA binding protein Rrp9.RNA19:701-711.

33. Sanduo Zheng#, Jia Wang#, Yingang Feng#,*, Jinfeng Wang andKeqiong 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 andKeqiong Ye*(2012) Crystal structure of Cmr2 suggests a nucleotide cyclase-related enzyme in type III CRISPR-Cas systems.FEBS Letters586:939-945.

37. Wei Zhang, Yang Zhao, Yan Guo andKeqiong 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 andKeqiong 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* andKeqiong 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 andKeqiong 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 andKeqiong Ye*(2011) Reconstitution and structural analysis of the yeast box H/ACA RNA-guided pseudouridine synthase.Genes Dev25:2409-2421.

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 andKeqiong 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 andKeqiong Ye*(2011) Structural basis of site-specific ribose methylation by box C/D RNA protein complexes.Nature469: 559-563.

46. Wei Zhang andKeqiong Ye*(2010) Progress in structural biology of RNA silencing.Chinese Bulletin of Life Sciences22: 608-615. (review in Chinese)

47. Lin Huang, Ping Yin, Xing Zhu, Yi Zhang andKeqiong 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 andKeqiong 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 andKeqiong Ye*(2009) Structural mechanism of substrate RNA recruitment in H/ACA RNA-guided pseudouridine synthase.Mol Cell34:427-439.

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 USA104:14640-14645.

53. Ling Li andKeqiong Ye*(2006) Crystal structure of an H/ACA box ribonucleoprotein particle.Nature443: 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.Structure13:1375-1384.

56. Ma, J.#,Ye, K#.and Patel, D.J. (2004) Structural mechanism of overhang-specific small interfering RNA recognition of the PAZ domain.Nature429:318-322.

57.Ye, K.,Malinina, L. and Patel, D.J. (2003) Recognition of small interfering RNA by a viral suppressor of RNA silencing.Nature426:874-878.

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.

(From Keqiong Ye, October 28, 2020)

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