教育经历
1996-1999 中国科学院上海生物化学研究所 博士
1989-1996 安徽农业大学 本科、硕士
工作经历
2021- 今 红宝石hbs最新网站hbs123 教授、副院长
2018-2020 红宝石hbs最新网站hbs123 教授、系主任
2008-2018 中国科学院上海植物生理生态研究所 研究员、课题组长
2000-2008 美国爱因斯坦医学院 博士后、研究助理
1999-2000 中国科学院上海生物化学研究所 研究助理
学术兼职
2023- 今 湖北省生理学会RNA生理与病理专业委员会主任
2022- 今 红宝石hbs最新网站hbs123泰康生命医学中心PI
2021- 今 中国生物物理学会理事
2020- 今 红宝石hbs最新网站hbs123RNA生物学研究所负责人
2011- 今 中国生物化学与分子生物学会RNA专业分会理事
主要科研奖励和个人荣誉
国家“杰出青年科学基金”(2015)
中国科学院“百人计划”(2009)
上海市科委“浦江人才”(2009)
Albert Einstein College of Medicine “Outstanding Postdoc” (2007)
承担课程
本科生:《生物化学》
研究领域
高等生物中内含子数量众多,在人类基因组中超过30万,需要通过RNA剪接加以去除。同时,RNA剪接也是基因表达调控网络中的重要环节,具有多样性和复杂性,与细胞分化、器官发育等生理过程密切相关,而剪接紊乱则是导致多种疾病发生的重要原因。我们以发育与疾病过程中RNA剪接的多样性与复杂性为研究重点,研究方向包括:
1)多种形式的RNA剪接发生与调控机制,如可变剪接、反式剪接和反向剪接;
2)次要剪接体的动态组装及次要内含子基因在神经退行性疾病中功能;
3)内含子中跨物种高度保守的顺式作用元件对器官发育、能量代谢的调控机制;
4)高频突变剪接因子在神经、代谢、肿瘤和血液性疾病发生发展中的作用机制;
5)环状RNA的生成机制与应用。
科研项目
2023-2025 国家自然科学基金委,国际合作与交流项目“染色质骨架蛋白调控反式剪接、可变剪接和可变多腺苷酸化的新功能与机制研究”,主持;
2021-2026 科技部,国家重点研发计划“纤维化进程中组织器官互作紊乱导致干细胞转录失调的机制研究”课题负责人;
2020-2023 国家自然科学基金委,面上项目“内含子区域的m6A修饰及其生物学功能研究”,主持;
2015-2017 中国科学院,重点部署项目“剪接体复合物的高效表达系统与作用机制研究”,首席;
2015-2017 国家自然科学基金委,重大研究计划“长非编码RNA表达的剪接调控机制”,主持。
代表性论文(*通讯作者)
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 - RNA14(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 Genetics16(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 Reports5: 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*, andXu 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 Biology32(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.