基因代謝的結構研究

我們研究在核糖核酸代謝中，扮演關 鍵角色的RNA 和DNA 結合蛋白質。 總體目標是闡明這些蛋白質在核糖 核酸代謝中的分子機制。我們主要運 用X 光晶體學的方法，來測定蛋白 質與核糖核酸結合的晶體三維結構， 配合生物化學和生物物理方法，來研 究這些蛋白質，如何以不同的方式展 開在RNA 和DNA 上的辨識、加工、 降解和修飾的作用機制。

我們們研究的大多數蛋白質的突變 和錯誤折疊，多與人類疾病相關，從 神經退行性疾病到發炎性和粒線體 疾病。因此了解這些蛋白質如何識別核糖核酸並參與核糖核酸代謝，以及它們如何喪失功能，不僅可以增進我們對核 糖核酸代謝機制的了解，也可以在疾病機制和治療上提供線索。

• Education
• Achievements & Honors
• Selected publications
• Lab members

• PDF, 1988-1992, Molecular Biology Institute UCLA, USA.
• Ph.D., 1988, Department of Chemistry University of Southern California, USA.
• BS, 1983, Department of Chemistry Tunghai University

• 1998, 中研院年輕學者研究成果獎
• 1998, 2003, 2011, 科技部傑出獎
• 2006-2010, 2011-2015, 2016-2000, 2021-2025, 中研院深耕計畫
• 2020, 教育部學術獎

1. Hsiao, Y.-Y., Fang, W.-H., Lee, C.-C, Chen, Y.-P., Hsu, P.-C., Yuan, H. S. (2014) Structural insights into DNA repair by RNase T, an exonuclease processing 3′ end of structured DNA in repair pathways. PLoS Biol. 12: e1001803.
2. Lin, J. L. J., Nakagawa, A., Skeen-Gaar, R., Yang, W.-Z., X., Ge, S., Mitani, Xue*, D, Yuan, H. S. (2016) Oxidative stress impairs cell death by repressing the nuclease activity of Endonuclease G. Cell Rep., 16: 279-287.
3. Lin, J.L.J., Wu, C.C., Yang, W.-Z., Yuan, H. S. (2016) Crystal structure of endonuclease G in complex with DNA reveals how it nonspecifically degrades DNA as a homodimer. Nucleic Acids Res. 44: 10480- 10490.
4. Huen, J., Lin, C.-L., Yi, W.-L., W.-Z. Yang, Golzarroshan, B., Yuan, H. S. (2017) Structural insights into a unique dimeric DEAD-box helicase CshA that promotes RNA decay. Structure 25: 469–481.
5. Golzarroshan, B., Lin, C.-L., Li, C.-L., Yang, W.-Z., Chu, L.-Y., Agrawal, S., Yuan, H. S. (2018) Crystal structure of dimeric human PNPase reveals why disease-linked mutants suffer from low RNA import and degradation activities. Nucleic Acids Res. 46: 8630-8640.
6. Wu, C.C., Lin, J.L.J., Yang-Yen, H.-F., Yuan, H. S. (2019) A unique exonuclease ExoG cleaves at the junction between RNA and DNA in mitochondrial DNA replication. Nucleic Acids Res. 47: 5405-5419.
7. Lin, C.C., Chen, Y. P., Yang, W. Z., Shen, J. C. K., Yuan, H. S. (2020) Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B. Nucleic Acids Res. 48: 3949-3961.
8. Wu, C.C., Lin, J.L.J., Yuan, H. S. (2020) Structures, mechanisms and functions of His-Me finger nucleases. Trends Biochem. Sci. 45: 935-946.