1980 - 1984  Zhejiang University, China, B.Sc. in Physics

1984 - 1989  Brandeis University, USA, M.A. (1985) & Ph.D. (1990) in Physics

1989 - 1991  Postdoctoral Fellow, Physics Department, University of Texas at Austin

1991 - 1993  Postdoctoral Associate, Physics Department, SUNY at Stony Brook

1993 - 1996  Visiting Scientist and Staff Associate, Cold Spring Harbor Laboratory

1996 - 2005  Assistant, Associate, and full Professor, Cold Spring Harbor Laboratory

2006 - 2008  Professor, Skirball Institute of Biomolecular Medicine & Department of Pharmacology, New York University School of Medicine

2008 -           Investigator, Institute of Biophysics, Chinese Academy of Sciences

The main research focus of our group is on structural studies of gene expression and regulation. Two themes of investigation include epigenetic control of gene transcription and mRNA processing:

1. Epigenetic control of gene expression

Epigenetic phenomena are stable inheritance of gene expression patterns controlled by higher order chromatin structure that depends on covalent modifications of DNA and histones. Epigenetic control of gene expression plays important roles in many biological processes, such as in cell type specifications during development, as well as in the development of many environment and age related diseases, such as cancer and diabetes. Our research in this area includes structural and functional studies of the catalytic mechanisms of histone modification enzymes, their substrate specificity, the mechanisms by which the enzymatic activities are regulated, the structural basis for the recognition of modified histones, and the mechanism of establishment and maintenance of higher chromatin structure in general. The results of our study will provide important mechanistic insights into the function of epigenetic inheritance in cell differentiation, epigenetic reprogramming in somatic cloning and iPS techniques, epigenetic deregulation in cancer and aging, and the development of therapeutics targeting epigenetic regulators.

2. RNA processing and protein-RNA interaction

Post-transcriptional mRNA processing includes 5’-capping, splicing and poly-adenylation at the 3’ end. Our current research focuses on mRNA splicing, as most human genes are alternatively spliced, which results in multiple proteins from a single transcript, thus, greatly increased the complexity of the human proteome. RNA splicing is carried out by the spliceosome, which is a large, dynamic complex composed of more than a hundred proteins and several small nuclear RNAs. Our goal is to elucidate the structural basis for splice sites selection and the molecular mechanism of RNA splicing, which include protein-protein and protein-RNA interaction within the spliceosome, and the interaction between the spliceosome, splicing factors and mRNA. In addition, mRNA splicing is coupled to transcriptional regulation, and our interest also includes structural and functional studies of protein-protein and protein-RNA interactions coupling the two processes.

1. Liu C.P.*, Yu Z., Xiong J., Hu J., Song A., Ding D., Yu C., Yang N., Wang M., Yu J., Hou P., Zeng K., Li Z., Zhang Z., Zhang X., Li W., Zhang Z.G., Zhu B.*, Li G.*, and Xu R.M.* (2023) Structural insights into histone binding and nucleosome assembly by chromatin assembly factor-1. Science 381, eadd8673.

2. Ge W., Yu C., Li J., Yu Z., Li X., Zhang Y., Liu C.P, Li Y., Tian C., Zhang X., Li G., Zhu B.*, and Xu R.M.* (2023) Basis of the H2AK119 specificity of the Polycomb repressive deubiquitinase. Nature 616, 176-182.

3. Yue Y., Yang W., Zhang L., Liu C.P., and Xu R.M. (2022) Topography of histone H3-H4 interaction with the Hat1-Hat2 acetyltransferase complex. Genes & Dev. 36, 408-413.

4. Zhang J., Zhang Y., You Q.L., Huang C., Zhang T.T., Wang M.Z., Zhang T.W., Yang X.C., Xiong J., Li Y.F., Liu C.P., Zhang Z.Q., Xu R.M.*, and Zhu B.* (2022) Highly enriched BEND3 prevents the premature activation of bivalent genes during differentiation. Science 375, 1053-1058.

5. Liu C.P.*, Jin W., Hu J., Wang M., Chen J., Li G., and Xu R.M.* (2021) Distinct histone H3-H4 binding modes of sNASP reveal the basis for cooperation and competition of histone chaperones. Genes & Dev. 35, 1610-1624.

6. Xu X., Wang M., Sun J., Yu Z., Li G., Yang N.*, and Xu R.M.* (2021) Structure specific DNA recognition by the SLX1-SLX4 endonuclease complex. Nucleic Acids Res. 49, 7740-7752.

7. Cao D., Han X., Fan X., Xu R.M.*, and Zhang X.* (2020) Structural basis for nucleosome-mediated inhibition of cGAS activity. Cell Res. 30, 1088-1097.

8. Jin W., Wang J., Liu C.P., Wang H.W.*, and Xu R.M.* (2020) Structural basis for pri-miRNA recognition by DROSHA. Mol. Cell 78, 423-433.

9. Song X., Yang L., Wang M., Gu Y., Ye B., Fan Z., Xu R.M.*, and Yang N.* (2019) A higher-order configuration of the heterodimeric DOT1L-AF10 coiled-coil domains potentiates their leukemogenic activity. Proc. Natl. Acad. Sci. USA 116, 19917-19923.

10. Zhang L., Serra-Cardona A., Zhou H., Wang M., Yang N., Zhang Z.G.*, Xu R.M.* (2018) Multisite Substrate Recognition in Asf1-Dependent Acetylation of Histone H3 K56 by Rtt109, Cell 174, 818-830.

(From Ruiming Xu, August 28, 2023)