Home CAS Center for Excellence


Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
Principal Investigators
WU Ligang
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: lgwu@@sibcb.ac.cn

Research Areas
Mechanisms of gene expression regulation by microRNA and RNAi

Research Interests

The cells of various eukaryotic organisms contain numerous small and long non-coding RNAs (ncRNA). However, to the majority of those ncRNAs, the questions as basic as whether they have functions and their regulatory mechanisms are still mysterious.  Our previous studies have shown that microRNA (miRNA) destabilize messages to which they are partially complementary by expediting poly(A) tail removal, and further identified CAF1 as the nuclease responsible for mRNA deadenylation mediated by miRNA and off-target RNAi caused by partially complementary siRNA. More recently, we revealed a new function of miRNA in the cells that miRNAs can serve as a surveillance system to repress nonsense mRNAs by recognizing miRNA-responsive elements in the open reading frame region downstream of the premature termination codon. We will continue to focus on discovering novel functions of ncRNAs and elucidating their molecular mechanisms in cell fate determination, which will allow us to develop advanced technology to manipulate gene expression for both basic research and therapeutic applications.
The current projects in this laboratory including:
1)      Studying mechanism of small non-coding RNA in gene regulation.
2)      Developing new strategy to improve the efficiency and specificity of RNAi and CRISPR.
3)      Using high-throughput screening method to identify the function of small and long non-coding RNA in cell fate determination and uncover the molecular mechanism.

Selected Publications

发表论文 (*通讯作者)

  1. Hua M,Liu W,Chen Y,Zhang F,Xu B,Liu S,Chen G*,Shi H* and  Wu L*. Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization. Cell Discovery. 2019 Feb 19. Doi: 10.1038/s41421-019-0087-9.[accepted]
  2. Zhao Y, Zhang Y, Teng Y, Liu K, Liu Y, Li W and Wu L* SpyCLIP: An easy-to-use and high-throughput compatible CLIP platform for characterization of protein-RNA interactions with high accuracy. Nucleic Acids Res. 2019 Jan 31. doi: 10.1093/nar/gkz049. [Epub ahead of print]
  3. Zhang F, Zhang Y, Lv X, Xu B, Zhang H, Yan J, Li H, Wu L*. Evolution of an X-linked miRNA family predominantly expressed in mammalian male germ cells. Mol Biol Evol. 2019 Jan 14. doi: 10.1093/molbev/msz001. [Epub ahead of print]
  4. Zhu Z, Zhang Y, Zhang Y, Zhang H, Liu W, Zhang N, Zhang X, Zhou G, Wu L*, Hua K*, Ding J*. Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAs in vitro. Hum Reprod. 2019 Feb 1;34(2):248-260. doi: 10.1093/humrep/dey344
  5. Zhang K, Zhang X, Cai Z, Zhou J, Cao R, Zhao Y, Chen Z, Wang D, Ruan W, Zhao Q, Liu G, Xue Y, Qin Y, Zhou B, Wu L, Nilsen T, Zhou Y, Fu XD. A novel class of microRNA-recognition elements that function only within open reading frames. Nat Struct Mol Biol. 2018 Nov;25(11):1019-1027. doi: 10.1038/s41594-018-0136-3.
  6. PMID: 30576496 Peng L, Zhang F, Shang R, Wang X, Chen J, Chou JJ, Ma J, Wu L*, Huang Y*. Identification of substrates of the small RNA methyltransferase Hen1 in mouse spermatogonial stem cells and analysis of its methyl-transfer domain. J Biol Chem. 2018 Jun 29;293(26):9981-9994.
  7. Long J, Huang C, Chen Y, Wu J, Shi S, Zhang Y, Wu L, Liu Y, Liu C and Lei M. Telomeric TERB1-TRF1 interaction is crucial for male meiosis. Nat Struct Mol Biol. 2017 Dec;24(12):1073-1080.
  8. Yao C, Yuan Q, Niu M, Fu H, Zhou F, Zhang W, Wang H, Wen L, Wu L, Li Z, He Z. Distinct Expression Profiles and Novel Targets of MicroRNAs in Human Spermatogonia, Pachytene Spermatocytes, and Round Spermatids between OA Patients and NOA Patients. Mol Ther Nucleic Acids. 2017 Dec 15;9:182-194.
  9. Chen X, Che D, Zhang P, Li X, Yuan Q, Liu TT, Guo J, Feng T, Wu L, Liao M, He Z, Zeng WX. Profiling of miRNAs in porcine germ cells during spermatogenesis. Reproduction. 2017 Dec;154(6):789-798..
  10. Gou LT, Kang J, Dai P, Wang X, Li F, Zhao S, Zhang M, Hua M, Lu Y, Zhu Y, Li Z, Chen H, Wu L, Li D, Fu X, Li J, Shi H, Liu M. Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis. Cell. 2017 Jun 1;169(6):1090-1104.e13.
  11. Qiu Y, Xu Y, Zhang Y, Zhou H, Deng YQ, Li XF, Miao M, Zhang Q, Zhong B, Hu Y, Zhang FC, Wu L, Qin CF, Zhou X. Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals. Immunity. 2017 Jun 20;46(6):992-1004.e5.
  12. Du H, Zhao Y, He J, Zhang Y, Xi H, Liu M, Ma J* and Wu L*. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun. (2016) 7:12626.DOI: 10.1038/ncomms12626
  13. Yang Q, Lin J, Liu M, Li R, Tian B, Zhang X, Xu B, Liu M, Zhang X, Li Y, Shi H*, Wu L*. Highly Sensitive Sequencing Reveals Dynamic Modifications and Activities of Small RNAs in Mouse Oocytes and Early Embryos. Sci Adv. (2016) Vol. 2, no. 6, e1501482 DOI: 10.1126/sciadv.1501482
  14. Shang R, Zhang F, Xu B, Xi H, Zhang X, Wang W, and Wu L*. Ribozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects. Nat Commun. 2015 Oct 12; 6:8430. DOI: 10.1038/ncomms9430
  15. Liu S, Zhang X, Shi C, Lin J, Chen G, Wu B, Wu L, Shi H, Yuan Y, Zhou W, Sun Z, Dong X, Wang J. Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome. J Transl Med. (2015) 13:238. doi: 10.1186/s12967-015-0605-y.
  16. Chen T, Hao Y, Zhang Y, Li M, Wang M, Han W, Wu Y, Lv Y, Hao J, Wang L, Li A, Yang Y, Jin K, Zhao X, Li Y, Ping X, Lai W, Wu L, Jiang G, Wang H, Sang L, Wang X, Yang Y, Zhou Q. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell. (2015) 16(3):289-301.
  17. Wu Y, Zhou H, Fan X, Zhang Y, Zhang M, Wang Y, Xie Z, Bai M, Yin Q, Liang D, Tang W, Liao J, Zhou C, Liu W, Zhu P, Guo H, Pan H, Wu C, Shi H, Wu L*, Tang F*, Li J*. Correction of a Genetic Disease by CRISPR-Cas9-Mediated Gene Editing in Mouse Spermatogonial Stem Cells.  Cell research. (2015) 25 (1):67-79. 
  18. Zhao Y, Lin J, Xu B, Hu S, Zhang X, and Wu L*. MicroRNA-mediated repression of nonsense mRNAs. Elife. (2014) Aug 8;3:e03032. Insight: "Stop the nonsense!"Elife. (2014) 3:e04300
  19. Gou L, Dai P, Yang J, Xue Y, Hu Y, Zhou Y, Kang J, Wang X, Li H, Hua M, Zhao S, Hu S, Wu L, Shi H, Li Y, Fu X, Qu L, Wang E, Liu M. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell research. (2014) 24: 680–700.
  20. Piao X, Zhang X, Wu L* and Belasco JG*. CCR4-NOT deadenylates mRNA associated with RNA-induced silencing complexes in human cells. Mol Cell Biol. (2010) 30(6): 1486-1494.
  21. Savas JN, Ma B, Deinhardt K, Culver BP, Restituito S, Wu L, Belasco JG, Chao MV, and Tanese N. A role for huntington disease protein in dendritic RNA granules. J Biol Chem. (2010) 285(17): 13142-13153.
  22. Wu L, Fan J, and Belasco JG. Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr Biol. (2008) 18(17): 1327-1332.
  23. Wu L, and Belasco JG. Examining the influence of microRNAs on translation efficiency and on mRNA deadenylation and decay. Methods Enzymol. (2008) 449: 373-393.
  24. Wu L, and Belasco JG. Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs. Mol Cell. (2008) 29(1): 1-7. (Invited Review)
  25. Bao L, Zhou M, Wu L, Lu L, Goldowitz D, Williams RW, and Cui Y. PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits. Nucleic Acids Res. (2007) 35(Database issue): D51-54.
  26. Wu L, Fan J, and Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A. (2006) 103(11): 4034-4039. Commentary: “MicroRNAs: new players in an old game.”, PNAS. (2006) 103(11):3951-2.Research Highlights: “Behind the scenes”  Nature Review Genetics, Nature Review Molecular Biology, (2006) 243(7).
  27. Wu L, and Belasco JG. Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells. Mol Cell Biol. (2005) 25(21): 9198-9208.
  28. Wu L, Fan J, Jiang L, Wang H, Song R, Zhang Q, Zhu H, Li N, Liu Z, and Xu Z. A specific cis-hairpin ribozyme facilitates infection of a TMV-based DNA vector in tobacco protoplasts. J Virol Methods. (2003) 111(2): 101-109.
  29. Wu L, Jiang L, Zhou Z, Fan J, Zhang Q, Zhu H, Han Q, and Xu Z. Expression of foot-and-mouth disease virus epitopes in tobacco by a tobacco mosaic virus-based vector. Vaccine. (2003) 21(27-30): 4390-4398.

Education Background & Academic Experience

2008-present:  Principle Investigator, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), CAS, Shanghai, China.
2001-2008:  Postdoctoral Fellow, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA.  
1996-2001:   Ph.D.     in Genetics, National Laboratory of Plant Molecular and Genetics, Shanghai Institute of Plant Physiology, The Chinese Academy of Sciences, Shanghai, China.
1992-1996:   B.S.       in Biochemistry Engineering, Department of Bioscience and Technology, Shanghai Jiao Tong University, Shanghai, China.

Research Team


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