表观遗传调控与干预重点实验室

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

2022年  药明康德生命化学研究奖

2021年  中源协和生命医学创新突破奖

2021年  中国科学院优秀导师奖

2021年  中国科学院大学领雁银奖

2020年  中国科学院优秀导师奖

2020年  国家杰出青年科学基金

2015年  国家优秀青年科学基金

2015年  海外高层次人才计划

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：

一、非编码RNA的功能机制研究

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它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），期望通过利用各种RNA功能基因组学手段，系统研究这些非编码RNA的功能机制及其实现的结构基础。

二、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。非编码RNA往往需要与RNA结合蛋白形成复合物以调控转录，因此研究RNA与蛋白质的相互作用位点和模式是探索非编码RNA功能机制的关键，也是我们课题组的重点关注方向。

三、RNA互作组学新技术开发

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，RNA的原位高级结构和作用靶标研究依然是领域内的瓶颈难题。我们将开发RNA空间互作组学新技术和计算新体系，以解决这些难题。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。

1. Liang Liang^#, Changchang Cao^#, Lei Ji^#, Zhaokui Cai^#, Di Wang, Rong Ye, Juan Chen, Xiaohua Yu, Jie Zhou, Zhibo Bai, Ruoyan Wang, Xianguang Yang, Ping Zhu, Yuanchao Xue*. Complementary Alu sequences mediate enhancer-promoter selectivity. Nature. 2023; 619(7971):868-875. (Highlight by Nature Reviews Genetics, 2023, 24: 588; Mol Cell, 2023; 83(18): 3234-3235)

2. Hailian Zhao^#, Zhaokui Cai^#, Jian Rao^#, Di Wu^#, Lei Ji, Rong Ye, Di Wang, Juan Chen, Changchang Cao, Naijing Hu, Ting Shu, Ping Zhu, Jianwei Wang*, Xi Zhou*, Yuanchao Xue*. SARS-CoV-2 RNA stabilizes host mRNAs to elicit immunopathogenesis. Mol Cell. 2023: S1097-2765(23)00978-4. (Featured Article; Cover story)

3. Rong Ye^#, Naijing Hu^#, Changchang Cao, Ruibao Su, Shihan Xu, Chen Yang, Xiangtian Zhou, Yuanchao Xue*. Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation. Mol Cell. 2023; 83(8): 1311- 1327.e7. (Featured Article; Preview by Mol Cell, 2023, 83(8): 1206-1207)

4. Jing Guo^#, Hailian Zhao^#, Jue Zhang^#, Xiangjiang Lv, Shen Zhang, Ruibao Su, Wei Zheng, Jing Dai, Fei Meng, Fei Gong, Guangxiu Lu, Yuanchao Xue*, Ge Lin*. Selective Translation of Maternal mRNA by eIF4E1B Controls Oocyte to Embryo Transition. Adv Sci. 2023; e2205500.

5. Hui Li, Hailian Zhao, Chunhui Yang, Ruibao Su, Min Long, Jinliang Liu, Lanying Shi, Yuanchao Xue*, You-Qiang Su*. LSM14B is an Oocyte-Specific RNA-Binding Protein Indispensable for Maternal mRNA Metabolism and Oocyte Development in Mice. Adv Sci. 2023; 10(18):e2300043.

6. Yigan Zhang^#, Jinyue Zhang^#, Yuanchao Xue*. ADAR1: a mast regulator of aging and immunity. Signal Transduct Target Ther. 2023; 8(1):7.

7. Rong Ye^#, Naijing Hu^#, Yuanchao Xue*. CRIC-seq protocol for in situ profiling of proximal RNA-RNA contacts associated with RNA-binding proteins. STAR Protoc. 2023; 4(3):102401.

8. Jianzhong Su^#, *, Jian Yuan^#, Liangde Xu^#, Shilai Xing^#, Mengru Sun^#, Yinghao Yao, Yunlong Ma, Fukun Chen, Longda Jiang, Kai Li, Xiangyi Yu, Zhengbo Xue, Yaru Zhang, Dandan Fan, Ji Zhang, Hui Liu, Xinting Liu, Guosi Zhang, Hong Wang, Meng Zhou, Fan Lyu, Gang An, Xiaoguang Yu; Myopia Associated Genetics and Intervention Consortium; Yuanchao Xue*, Jian Yang*, Jia Qu*. Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population. Cell Rep. 2023; 42(5):112510.

9. Peng Wang^#, Qiushi Wang^#, Lianwan Chen^#, Zheng Cao^#, Hailian Zhao, Ruibao Su, Ning Wang, Xiaojing Ma, Jin Shan, Xinyan Chen, Qi Zhang, Baochen Du, Zhiheng Yuan, Yanmei Zhao*, Xiaorong Zhang*, Xuejiang Guo*, Yuanchao Xue*, Long Miao*. RNA-binding protein complex AMG-1/SLRP-1 mediates germline development and spermatogenesis by maintaining mitochondrial homeostasis in Caenorhabditis elegans. Sci Bull. 2023; 68(13):1399-1412.

10. Yue Lv^#, Gang Lu^#, Yuling Cai^#, Ruibao Su^#, Liang Liang, Xin Wang, Wenyu Mu, Xiuqing He, Tao Huang, Jinlong Ma, Yueran Zhao, Zi-Jiang Chen*, Yuanchao Xue*, Hongbin Liu*, Wai-Yee Chan*. RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits. Protein Cell. 2022; 14(1):51-63.

11.Yuanchao Xue*. Architecture of RNA-RNA interactions. Curr Opin Genet Dev. 2022; 72:138-144.

12. Di Wang^#, Rong Ye^#, Zhaokui Cai, Yuanchao Xue*. Emerging roles of RNA-RNA interactions in transcriptional regulation (Invited review). WIRES RNA. 2022; 18:e1712.

13. 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. (Best of BMB in 2021)

14. 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.

15. 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, 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.

16. 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. (Highlight by Nature Methods, 2020, 17, 760; Recommended in Faculty Opinions)

17. 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 Res. 2018; 28: 981-995. (Cover story; highlight by Cell Res, 2018 (10): 963-964)

18. Jinyang Zhang^#, Lingling Hou^#, Zhenqiang Zuo^#, Peifeng Ji, Xiaorong Zhang, Yuanchao Xue, Fangqing Zhao*. Comprehensive profiling of circular RNAs with nanopore sequencing and CIRI-long. Nat Biotechnol. 2021; 39(7):836-845.

19.Yuanchao Xue, Runsheng Chen*, Lianghu Qu*, Xiaofeng Cao*. Noncoding RNA: from dark matter to bright star. Science China Life sciences. 2020; 63, 463-468.

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

21.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. Nat Neurosci. 2016; 19(6):807-15.

22. Juan Chen^#, Yuanchao Xue*. Emerging roles of non-coding RNAs in epigenetic regulation. Sci China Life Sci. 2016; 59(3):227-35.

23.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. (Highlight by Nature, 2013, 493: 275; Science, 2013, 339: 374; Nature Reviews Neuroscience, 2013, 14, 155)

24.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. Mol Cell. 2009; 36(6):996-1006. (Cover story; Preview by Mol Cell, 2009;36(6):918-9)

（资料来源：薛愿超研究员，2024-2-6）