Research Area
The main research focus of our group is to understand how small regulatory RNA or DNA mediates prokaryotic defense against invasion by foreign nucleic acids. The main focus of our work is to systematically demonstrate the mechanisms of 1) the CRISPR-Cas system, and 2) Argonaut (Ago) protein-mediated RNA/DNA interference. Our research in CRISPR-Cas system includes the molecular mechanism of spacer acquisition, pre-crRNA processing and RNA-guided DNA/RNA cleavage. The overall goal of our studies of the CRISPR-Cas system is to gain important insights into the structural-functional relationship of the processes prokaryotes use to fight invading nucleic acids. Our long-term goals in studying Ago protein-mediated DNA interference are to structurally characterize and mechanistically define events associated with RNA or DNA interference.
Team Description
Our team is made up of great students and research fellows. They has won a lot of Awards, for example, Cheng Zhi has won the 2020 Di Ao Scholarship and National master scholarship. You Lilan, has won the Special Award of Chinese Academy of Science and National master scholarship in 2019. Li Xueyan, has won the 2018 Outstanding Award of director of Chinese Academy of Science.
Team Members
Team Show
Publications
1. Huang X, Sun W, Cheng Z, Chen M, Li X, Wang J, Sheng G*, Gong W* and Wang Y*. Structural basis for two metal-ion catalysis of DNA cleavage by Cas12i2. Nature Communications, 2020.10, online.
2. Sun W#, Yang J#, Cheng Z#, Amrani N, Liu C, Wang K, Ibraheim R, Edraki A, Huang X, Wang M, Wang J, Liu L, Sheng G, Yang Y, Lou J, Sontheimer E*, and Wang Y*. Structures of Neisseria meningitidis Cas9 Complexes in Catalytically Poised and Anti-CRISPR-Inhibited States. Molecular Cell, 2019, 76(6): 938-952.
3. You L, Ma J, Wang J, Artamonova D, Wang M, Liu L, Xiang H, Severinov K, Zhang X*, Wang Y*. Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference. Cell, 2019, 176, 239–253.
4. Liu L, Yin M, Wang M, Wang Y*. Phage AcrIIA2 DNA Mimicry: Structural Basis of the CRISPR and Anti-CRISPR Arms Race. Molecular Cell, 2019, 73, 611–620.
5. Lei J, Sheng G, Peter Pak-Hang Cheung, Wang S, Li Y, Gao X, Zhang Y*, Wang Y*, Huang X*. Two symmetric arginine residues play distinct roles in Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage, PNAS, 2019，116: 845–853.
6. Chang L#, Sheng G#, Zhang Y#, Shao S, Wang Y* and Sun Y*. AgoFISH: cost-effective in situ labelling of genomic loci based on DNA-guided dTtAgo protein. Nanoscale Horizons, 2019, 4:918-923.
7. Thavalingam A, Cheng Z, Garcia B, Huang X, Shah M, Sun W, Wang M, Harrington L, Hwang Sungwon Y, Reyes H, Sontheimer E, Doudna J, Davidson A, Moraes T*, Wang Y*, Maxwell K*. Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2. Nature Commun., 2019, 26;10(1):2806.
8. Yin M, Wang J, Wang M, Li X, Zhang M, Wu Q, Wang, Y. Molecular mechanism of directional CTCF recognition of a diverse range of genomic sites. Cell Research, 2017, 27(11):1365-1377.
9. Liu L, Li X, Ma J, Li Z, You L, Wang J, Wang M, Zhang X, Wang, Y. The Molecular Architecture for RNA-Guided RNA Cleavage by Cas13a. Cell, 2017. 170(4):714-726.
10. Sheng G, Gogakos T, Wang J, Zhao, H, Serganov A, Juranek S, Tuschl T, Patel D, Wang, Y. Structure/cleavage-based insights into helical perturbations at bulge sites within T. thermophilus Argonaute silencing complexes. Nucleic Acids Res. 2017, 45(15):9149-9163.
11. Liu L, Li X, Wang J, Yin M, Chen P, Wang M, Li J, Sheng G, Wang Y. Two Distant Catalytic Sites Are Responsible for C2c2 RNase Activities. Cell. 2017,168:121-134.
12. Liu L, Chen P, Wang M, Li X, Wang J, Yin M, Wang Y. C2c1-sgRNA Complex Structure Reveals RNA-guided DNA Cleavage Mechanism. Molecular Cell. 2017, 65.
13. Swarts D, Szczepaniak M, Sheng G, Chandradoss S, Zhu Y, Timmers E, Zhang Y, ZhaoH, Lou J, Wang Y, Joo C and Oost J. Autonomous Generation and Loading of DNA Guides by Bacterial Argonaute，Molecular Cell, 2017, 65(6):985-998.
14. Wang J, Ma J, Cheng Z, Meng X, You L, Wang M, Zhang X, Wang, Y. A CRISPR evolutionary arms race: structural insights into viral anti-CRISPR/Cas responses. Cell Research. 2016, 26:1165–1168.
15. Wang, J., Li, J., Zhao, H., Sheng, G., Wang, M., Yin, M. & Wang, Y., Structural and Mechanistic Basis of PAM-Dependent Spacer Acquisition in CRISPR-Cas System. Cell. 2015, 163: 840-853.
16. Zhao, H., Sheng, G., Wang, J., Wang, M., Bunkoczi, G., Gong, W., Wei, Z. & Wang, Y. “Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli”, Nature. 2014, 151: 147-150.
17. Swarts, D. C., Makarova, K., Wang, Y., Nakanishi, K., Ketting, R., Koonin, E., Patel, D. J. & Oost, van der, J., “The evolutionary journey of Argonaute proteins”, Nature structural & molecular biology, 2014, 21: 743-753.
18. Swarts, D. C., Jore, M. M., Westra, E. R., Zhu, Y., Janssen, J. H., Snijders, A. P., Wang, Y., Patel, D. J., Berenguer, J., Brouns, S. J.J. & Oost, van der, J. "DNA-guided DNA interference by a prokaryotic Argonaute", Nature, 2014, 507: 258-261.
19. Sheng, G., Zhao, H., Wang, J., Rao, Y., Tian, W., Swarts, D. C., van der Oost, J., Patel, D. J. and Wang, Y. "Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage." Proc Natl Acad Sci U S A.2014, 111(2): 652-657.
20. Rüdel S, Wang, Y, Lenobel R, K?rner R, Hsiao HH, Urlaub H, Patel D, Meister G. Phosphorylation of human Argonaute proteins affects small RNA binding. Nucleic Acids Res.2011,39:2330-43.
21. Wang, Y., Ludwig J., Schuberth C., Goldeck M., Schlee M., Li H., Juranek S., Sheng G., Micura R., Tuschl T., Hartmann G., Patel D., Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I. Nat Struct Mol Biol. 2010, 17:781-7.. 2010, 17:781-7.
22. Wang, Y, Juranek S, Li H, Sheng G, Tuschl T, Patel DJ. Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes. Nature. 2009, 461:754-761.
23. Wang, Y, Juranek S, Li H, Sheng G, Tuschl T, Patel DJ. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature. 2008, 56:921-926.
24. Wang, Y, Sheng G, Juranek S, Tuschl T, Patel DJ., Structure of the guide-strand-containing argonaute silencing complex. Nature. 2008, 456:209-213.
25. Wang, Y, Liu L, Wei Z, Cheng Z, Lin Y, Gong W. Seeing the process of histidine phosphorylation in human bisphosphoglycerate mutase. J Biol Chem. 2006, 281:39642-8.
26. Wang, Y, Wei Z, Liu L, Cheng Z, Lin Y, Ji F, Gong W. Crystal structure of human B type phosphoglycerate mutase bound with citrate. Biochem. Biophys. Res. Commun. 2005, 331:1207-15.
27. Wang, Y, Wei Z, Bian Q, Cheng Z, Wan M, Liu L, Gong W，Crystal structure of human bisphosphoglycerate mutase, J. Biol. Chem. 2004, 279: 39132-8.