许瑞明——中国科学院生物物理研究所

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 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.
代表性论文 (Selected Publications)

(1)  J. Han, H. Zhou, B. Horazdovsky, K. Zhang, R.M. Xu, and Z. Zhang (2007) Rtt109 acetylates histone H3 lysine 56 and functions in DNA replication. Science 315, 653-655.
(2) Y. Huang, J. Fang, M.T. Bedford, Y, Zhang and R.M. Xu (2006) Recognition of histone H3 Lysine-4 methylation by a domain-swapped double tudor domain of JMJD2A. Science 312, 748-751.
(3) H.C. Hsu, B. Stillman, and R.M. Xu (2005) Structural basis for origin recognition complex 1 protein-silencing regulator 1 protein interaction in epigenetic silencing. Proc. Natl. Acad. Sci. USA 102, 8519-8524.
(4) H. Shi, O. Cordin, C.M. Minder, P. Linder, and R.M. Xu (2004) Crystal Structure of the ATP-dependent splicing and export factor UAP56. Proc. Natl. Acad. Sci. USA 101, 17628-17633.
(5) J. Min, Y. Zhang, and R.M. Xu (2003) Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at lysine 27. Genes & Dev. 17, 1823-1828.
(6) H. Shi and R.M. Xu (2003) Crystal Structure of the Drosophila Mago nashi-Y14 Complex. Genes & Dev. 17, 971-976.
(7) J. Min, Q. Feng, Z. Li, Y, Zhang, and R.M. Xu (2003) Structure of the catalytic domain of human Dot1L, a non-SET domain nucleosomal histone methyltransferase. Cell 112, 711-723.
(8) J. Min, X. Zhang, X. Cheng, S.I. Grewal, and R. M. Xu (2002) Structure of the SET domain histone lysine methyltransferase Clr4. Nature Struct. Biol. 9, 828-832.
(9) Z. Zhang, M.K. Hayashi, O. Merkel, B. Stillman, and R.M. Xu (2002) Structure and function of the BAH domain of ORC1 in transcriptional silencing. EMBO J. 21, 4600-4611.
(10) J. Min, J. Landry, R. Sternglanz, and R.M. Xu (2001) Crystal structure of a SIR2 homolog-NAD complex. Cell 105, 269-279.