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Professor at the Department of Biochemistry
Laboratory of RNA Splicing and Diseases
Vice Dean at the College of Life Sciences
Principle Investigator at the Taikang Center for Life and Medical Sciences
Director of the RNA Institute
Wuhan University
Wuhan 430072, China
Tel: 027-68789348
E-mail: yongzhen.xu@whu.edu.cn
Research Interests:
RNA splicing removes large numbers of introns in higher eukaryotes, for example, there are over 300,000 introns in the human genome. The dynamic assembly of the spliceosome and the diversified types of intron selection are critical for the regulation of gene expression, closely related to physiological processes such as cell differentiation and organ development. Importantly, the aberrant splicing results in various human diseases. We are interested in the regulatory mechanisms of RNA splicing during the development and diseases and focus on the below directions:
1) Regulatory mechanisms of alternative splicing, trans-splicing, and back-splicing;
2) The dynamic assembly of minor spliceosomes and the function of minor intron-containing genes in neurodegenerative diseases;
3) Regulatory functions of the highly conserved intronic cis-elements across species on organ development and energy metabolism;
4) Regulatory mechanisms of splicing factors with high-frequent mutations in the occurrence and development of neurological, metabolic, tumor, and hematological diseases;
5) Biogenesis, functions, and applications of circular RNAs.
Representative Publications （* corresponding author）
1) Li H, Ding Z, Fang ZY, Long N, Ang HY, Zhang Y, Fan YJ*, and Xu YZ* (2024) Conserved intronic secondary structures with concealed branch sites regulate alternative splicing of poison exons. Nucleic Acids Research DOI: 10.1093/nar/gkae185, PMID: 38499485.
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 19(11): e1011021, PMID: 37917726.
3) 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, PMID: 37070178.
4) Ding Z, Meng YR, Fan YJ, and Xu YZ* (2023) Roles of minor spliceosome in intron recognition and the convergence with the better understood major spliceosome. Wiley Interdisciplinary Review - RNA 14(1): e1761, PMID: 36056453, Advance review.
5) Gui X, Zhang P, Wang D, Ding Z, Wu X, Shi J, Shen QH, Xu YZ, Ma W, and Qiao Y* (2022) Phytophthora effector PSR1 hijacks the host pre-mRNA splicing machinery to modulate small RNA biogenesis and plant immunity. Plant Cell 34(9): 3443-3459, PMID: 35699507.
6) Tang P, Yang Y, Li G, Huang L, Wen M, Ruan W, Guo X, Zhang C, Zuo X, Luo D, Xu YZ, Fu XD*, and Zhou Y* (2022) Alternative polyadenylation by sequential activation of distal and proximal PolyA sites. Nature Structural & Molecular Biology 29(1): 21-31, PMID: 37661812.
7) 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, PMID: 34723968.
8) 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, PMID: 33154379. Recommended in the focus of “From Brain to Behaviour”.
9) 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(11): 5799-5813, PMID: 32399566. Selected as “Breakthrough Article”.
10) Cheng L, Zhang Y, Zhang Y, Chen T, Xu YZ, and Rong YS* (2020) Loss of the RNA trimethylguanosine cap is compatible with nuclear accumulation of spliceosomal snRNAs but not pre-mRNA splicing or snRNA processing during animal development. PLOS Genetics 16(10): e1009098, PMID: 33085660.
11) 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(6): 809-820, PMID: 30836863.
12) Lv M, Yao Y, Li F, Xu L, Yang L, Gong Q, Xu YZ, Shi Y, Fan YJ*, Tang Y* (2019) Structural insights reveal the specific recognition of roX RNA by the dsRNA-binding domains of the RNA helicase MLE and its indispensable role in dosage compensation in Drosophila. Nucleic Acids Research 47(6): 3142-3157, PMID: 30649456.
13) 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(24): 2710-2723, PMID: 28087715.
14) 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(7): 760-771, PMID: 25838544.
15) 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, PMID: 24290758.
16) 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(8): 4660-4670, PMID: 23462954.
17) 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(7), 1395-1407, PMID: 22627775.
18) 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(2): 470-478, PMID: 22064476.
19) Xu YZ and Query CC (2007) Competition between the ATPase Prp5 and branch region-U2 snRNA pairing modulates the fidelity of spliceosome assembly. Molecular Cell 28(5): 838-849, PMID: 18082608.
20) Xu YZ, Newnham CM, Kameoka S, Huang T, Konarska MM, and Query CC (2004) Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA. The EMBO Journal 23(2): 376-385, PMID: 14713954.
