杰出青年科学基金获得者

简       历：

　　2000 - 2004  信阳师范学院，获理学学士学位

　　2004 - 2010  武汉大学，获理学博士学位

　　2010 - 2015  美国加州大学圣地亚哥分校，博士后

　　2015 - 至今  中国科学院生物物理研究所，研究员，博士生导师

　　2016 - 至今  中国科学院大学，岗位教授

获奖及荣誉：

社会任职：

研究方向：

　　本研究组围绕RNA结合蛋白和非编码RNA，主要关注RNA-蛋白质复合物在转录和表观遗传层面如何调控基因表达，以及如何在细胞分化、转分化和癌症发生等命运决定过程中发挥作用。主要研究内容包括：

　　1、RNA结合蛋白的转录调控机制

　　RNA结合蛋白可在转录和转录后水平调控基因表达。除核酶外，绝大多数RNA需要与RNA结合蛋白形成复合物以发挥生物学功能，因此研究RNA与蛋白质的相互作用位点和模式是探索RNA功能的关键。我们关注RNA结合蛋白PTB，该家族共有三个成员：PTBP1（PTB）、PTBP2（nPTB）和PTBP3（ROD1）。它们都有4个与RNA结合的RRM结构域，氨基酸有～74%的相似度，但是功能却不相同，而且表达的组织特异性也不一样。我们将重点研究该蛋白家族成员在细胞分化和转分化过程中的转录调控机制。

　　2、非编码RNA的功能与作用机制研究

　　人类基因组的广泛转录产生了海量的非编码RNA，它们虽然也携带遗传信息，但是往往不具备蛋白质编码潜能，其调控功能主要通过形成复杂的高级结构并与其他RNA分子相互作用而实现。我们重点关注增强子RNA（enhancer RNA, eRNA）、启动子RNA（promoter upstream antisense RNA, uaRNA）和长链非编码RNA(long noncoding RNA)，期望通过开发和利用多种RNA功能基因组学手段，系统研究这些非编码RNA的生理功能与致病机理。

　　3、RNA-Protein研究的新技术开发

　　RNA在体内以高级结构形式存在，RNA结构的动态变化对于遗传信息的精确传递至关重要，目前缺乏实验方法在基因组范围内解析RNA的原位高级结构。此外，研究RNA结合蛋白的经典CLIP-seq方法需要大量的细胞，无法解决细胞的异质性和个别细胞数目稀缺的问题，因此亟待开发单细胞的功能基因组学研究方法。

承担项目情况：

代表论著：

1. Changchang Cao^#, Zhaokui Cai^#, Xia Xiao^#, Jian Rao, Juan Chen, Naijing Hu, Minnan Yang, Xiaorui Xing, Yongle Wang, Manman Li, Bing Zhou, Xiangxi Wang, Jianwei Wang*, Yuanchao Xue*. The architecture of the SARS-CoV-2 RNA genome inside virion. Nat Commun., 2021, 12(1): 3917.

2. Changchang Cao^#, Zhaokui Cai^#, Rong Ye, Ruibao Su, Naijing Hu, Hailian Zhao, Yuanchao Xue*. Global in situ profiling of RNA-RNA spatial interactions with RIC-seq. Nat Protoc., 2021, 16(6): 2916-2946.

3. Ruibao Su^# , Li-Hua Fan^#, Changchang Cao^# , Lei Wang, Zongchang Du, Zhaokui Cai, Ying-Chun Ouyang, Yue Wang, Qian Zhou, Ligang Wu, Nan Zhang, Xiaoxiao Zhu, Wen-Long Lei, Hailian Zhao, Yong Tian, Shunmin He 1, Catherine C L Wong*, Qing-Yuan Sun*, Yuanchao Xue*. Global profiling of RNA-binding protein target sites by LACE-seq. Nat Cell Biol., 2021, 23(6): 664-675.

4. Rong Ye, Changchang Cao, Yuanchao Xue*. Enhancer RNA: biogenesis, function, and regulation. Essays Biochem, 2020, 64(6): 883-894.

5. Hao Qian, Xinjiang Kang, Jing Hu, Dongyang Zhang, Zhengyu Liang, Fan Meng, Xuan Zhang, Yuanchao Xue, Roy Maimon, Steven F Dowdy, Neal K Devaraj, Zhuan Zhou, William C Mobley, Don W Cleveland, Xiang-Dong Fu. Reversing a model of Parkinson's disease with in situ converted nigral neurons. Nature, 2020, 582(7813): 550-556.

6. Zhaokui Cai^#; Changchang Cao^#; Lei Ji^#; Rong Ye; Di Wang; Cong Xia; Sui Wang; Zongchang Du; Naijing Hu; Xiaohua Yu; Juan Chen; Lei Wang; Xianguang Yang; Shunmin He; Yuanchao Xue*. RIC-seq for global in situ profiling of RNA-RNA spatial interactions, Nature, 2020, 582, 432-437

7. Juan Chen^#, Zhaokui Cai^#, Meizhu Bai^#, Xiaohua Yu^#, Chao Zhang^#, Changchang Cao, Xihao Hu, Lei Wang, Ruibao Su, Di Wang, Lei Wang, Yingpeng Yao, Rong Ye, Baidong Hou, Yang Yu, Shuyang Yu, Jinsong Li, Yuanchao Xue*. The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes. Cell Research, 2018, 28: 981-995 (Cover story).

8. Yuanchao Xue^#*, Hao Qian^#, Jing Hu, Bing Zhou, Yu Zhou, Xihao Hu, Aziz Karakhanyan, Zhiping Pang, Xiang-Dong Fu*. Sequential Regulatory Loops as Key Gatekeepers for Neuronal Reprogramming in Human Cells. Nature Neuroscience 2016, 19(6): 807-15. doi: 10.1038/nn.4297.

9. Ashleigh E Schaffer, Veerle R C Eggens, Ahmet Okay Caglayan, Miriam S Reuter, Eric Scott, Nicole G Coufal, Jennifer L Silhavy, Yuanchao Xue, Hulya Kayserili , Katsuhito Yasuno, Rasim Ozgur Rosti, Mostafa Abdellateef, Caner Caglar, Paul R Kasher, J Leonie Cazemier, Marian A Weterman, Vincent Cantagrel, Na Cai, Christiane Zweier, Umut Altunoglu, N Bilge Satkin, Cengiz Yalcinkaya, Huseyin Caksen, Kaya Bilguvar, Xiang-Dong Fu, Christopher R Trotta, Stacey Gabriel, André Reis, Murat Gunel, Frank Baas, Joseph G Gleeson*. CLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration. Cell, 2014, 157, 1-13.

10. Hong Ouyang^#, Yuanchao Xue, Ying Lin, Xiaohui Zhang, Lei Xi, Sherrina Patel, Huimin Cai, Jing Luo, Meixia Zhang, Ming Zhang, Yang Yang, Gen Li, Hairi Li, Wei Jiang, Emily Yeh, Jonathan Lin, Michelle Pei, Jin Zhu, Guiqun Cao, Liangfang Zhang, Benjamin Yu, Shaochen Chen, Xiang-Dong Fu*, Yizhi Liu*, Kang Zhang*. WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis. Nature, 2014, 511(7509): 358-361.

11. Yuanchao Xue^#, Kunfu Ouyang, Jie Huang, Yu Zhou, Hong Ouyang, Hairi Li, Gang Wang, Qijia Wu, Chaoliang Wei, Yanzhen Bi, Li Jiang, Zhiqiang Cai, Hui Sun, Kang Zhang, Yi Zhang, Ju Chen, Xiang-Dong Fu*. Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits. Cell, 2013, 152 (1-2): 82-96.

12. Yuanchao Xue^#, Yu Zhou^#, Tongbin Wu, Tuo Zhu, Xiong Ji, Young-SooKwon, Chao Zhang, Gene Yeo, Douglas L. Black, Hui Sun, Xiang-Dong Fu*, Yi Zhang*, Genome-wide Analysis of PTB-RNA Interactions Reveals a Strategy Used by the General Splicing Repressor to Modulate Exon Inclusion or Skipping. Molecular Cell, 2009, 36(6): 996-1006 (Cover story).

（资料来源：薛愿超研究员，2021-07-01）