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E-mail: Yongzhen.Xu@whu.edu.cn Website: https://xu-lab-whu.github.io
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Biography
Education:
1989-1996 Anhui Agriculture University, China (B.S. & M.S. in Agriculture)
1996-1999 Shanghai Institute of Biochemistry, Chinese Academy of Sciences (Ph.D. in Biochemistry and Molecular Biology)
Scientific experience:
2000-2008 Albert Einstein College of Medicine, USA (Postdoc and Research Associate in the Department of Cell Biology)
2008-2018 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (Principal Investigator, Professor)
2018-2020 College of Life Sciences, Wuhan University (Professor and Chair at the Department of Biochemistry)
2021-present College of Life Sciences, Wuhan University (Vice Dean, Professor at the Department of Biochemistry)
2022-present TaiKang Center for Life and Medical Sciences, Wuhan University (Principal Investigator)
Research
RNA splicing, removal of introns, is an essential step for both coding and non-coding genes during the eukaryotic RNA processing. RNA splicing is catalyzed by the spliceosome, a large and dynamic macromolecular machine that consists of five small nuclear RNAs and >100 proteins. Both splicing fidelity and efficiency are important for generating accurate mRNAs, and thereby functional proteins. Including alternative splicing, trans-splicing, back splicing and minor splicing, diverse selection of splice sites and introns generate multiple RNA isoforms from one gene, which is critical for the regulation of cell development and differentiation. Furthermore, aberrant splicing that caused by mutations in splicing factors or RNA cis-elements has been found in many diseases.
Our group has been interested in:
1) Regulatory mechanism in alternative splicing, trans-splicing, back splicing and minor splicing;
2) Splicing regulation in development and diseases;
3) Splicing proofreading by ATPases/RNA helicases;
4) Coupling between splicing and transcription, chromatin remodeling;
5) Conserved intronic motifs and structures.
Representative Publications
: contribute equally, * : corresponding author.
1. Fan YJ#*, Ding Z#, Zhang Y#, Su R, Yue JL, Liang AM, Huang QW, Meng YR, Li M, Xue Y and Xu YZ* (2023) Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs. Nucleic Acids Research 51(10): 5228-5241.
2. Wang M#, Liang AM#, Zhou ZZ, Pang TL, Fan YJ* and Xu YZ* (2023) Deletions of singular U1 snRNA gene significantly interfere with transcription and 3'-end mRNA formation. PLOS Genetics DOI: 10.1371/journal.pgen.1011021.
3. Ding Z, Meng YR, Fan YJ, Xu YZ* (2022) Roles of minor spliceosome in intron recognition and the convergence with the better understood major spliceosome. WIREs RNA e1761.
4. Zhang B#, Ding Z#, Li L, Xie LK, Fan YJ and Xu YZ* (2021) Two oppositely-charged sf3b1 mutations cause defective development, impaired immune response, and aberrant selection of intronic branch sites in Drosophila. PLoS Genetics 17(11): e1009861.
5. Li L, Ding Z, Pang TL, Zhang B, Li CH, Liang AM, Wang YR, Zhou Y, Fan YJ* and Xu YZ* (2020) Defective minor spliceosomes induce SMA-associated phenotypes through sensitive intron-containing neural genes in Drosophila. Nature Communications 11(1):5608.
6. Shao W, Ding Z, Zheng ZZ, Shen JJ, Shen YX, Pu J, Fan YJ, Query CC* and Xu YZ* (2020) Prp5–Spt8/Spt3 interaction mediates a reciprocal coupling between splicing and transcription. Nucleic Acids Research 48, 5799–5813.
7. Zheng ZZ, Sun X, Zhang B, Pu J, Jiang ZY, Li M, Fan YJ and Xu YZ* (2019) Alternative splicing regulation of doublesex gene by RNA-binding proteins in the silkworm Bombyx mori. RNA Biology 16: 809-820.
8. Qiu C#, Zhang Y#, Fan YJ#, Pang TL, Su Y, Zhan S* and Xu YZ* (2019) HITS-CLIP reveals sex-differential RNA binding and alterative splicing regulation of SRm160 in Drosophila. J Mol Cell Biol 11: 170-181.
9. Tang Q#, Rodriguez-Santiago S#, Wang J, Pu J, Yuste A, Gupta V, Moldón A, Xu YZ* and Query CC* (2016) SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing. Genes & Development 30: 2710-2723.
10. Gao JL#, Fan YJ#, Wang XY#, Zhang Y, Pu J, Li L, Shao W, Zhan S, Hao J and Xu YZ* (2015) A conserved intronic U1 snRNP-binding sequence promotes trans-splicing in Drosophila. Genes & Development 29, 760-771.
11. Zhang ZM#, Yang F#, Zhang J, Tang Q, Li J, Gu J, Zhou J* and Xu YZ* (2013) Crystal structure of Prp5p reveals interdomain interactions that impact spliceosome assembly. Cell Reports 5, 1269-1278.
12. Yang F, Wang XY, Zhang ZM, Pu J, Fan YJ, Zhou J, Query CC and Xu YZ* (2013) Splicing proofreading at 5' splice sites by ATPase Prp28p. Nucleic Acids Research 41, 4660-4670.
13. Shao W#, Zhao QY#, Wang XY, Xu XY, Li MW, Li X* and Xu YZ* (2012) Alternative splicing and trans-splicing events revealed by analysis of the Bombyx mori transcriptome. RNA 18, 1395-407.
14. Shao W, Kim HS, Cao Y, Xu YZ* and Query CC* (2012) A U1–U2 snRNP interaction network during intron definition. Molecular and Cellular Biology 32, 470-478.