系統化分析RNA剪接與轉譯

後轉錄調節是提升基因表現的細膩度，使高等生物如人類高度複雜化的最重要因素。基因轉錄只是基因表現的第一步，DNA 被轉錄成 pre-mRNA 後，佔高達約九成的內含子(intron)序列需被移除，而剩餘的外顯子(exon)則需被正確的剪接起來，這個過程稱作 RNA 剪接。 這是一個具備驚人的精準度且需要高度調節的過程。RNA 剪接完成後會運送到細胞各處，在適當的時機轉譯成蛋白質。在這個過程中活性很高的RNA 必須被保護住以保持其序列的完整，且在接收到轉譯的指令之前抑制轉譯活性。 mRNA 的非轉譯區(untranslated region)帶有許多調節 RNA 穩定性與轉譯活性的資訊，蛋白質以及microRNA 可藉由辨認這些資訊來調控 RNA 的活性。

近年發現RNA 的調控不但豐富多元且是決定細胞命運的重要因子，許多疾病也被發現是因 RNA 調控失衡而導致。因此，我們發展高通量合成實驗的方法，可以同時檢測上萬種不同的基因序列對剪接的影響。 藉由新的 RNA 定序技術，並結合生物實驗及電腦演算法，系統化地分析內含子與非轉譯區的基因變異如何透過調控 RNA 的活性。我們透過大量的資料找到調控 RNA 命運的決定因素，了解人類天然的基因變異如何藉由影響剪接而導致疾病發生，有助於預測未知突變的影響，作為精準醫療的基礎。

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

• PDF, 2012-2016, Dept. Mol. Cell. Bio. & Biochem., Brown Univ., USA
• Ph.D., 2005-2012, Mol. Medicine, Univ. Mass. Medical School, USA
• MS, 2002-2003, Neuroscience, Univ. College London, UK
• BS, 1998-2002, Dept. Zoology, Natl.Taiwan Univ. Taiwan

• 2017-2019, Initial Employment Academic Research Grants 中研院新聘學術獎, Academia Sinica, Taiwan
• 2017-2020, MOST Talented Scholar Fellowship 科技部延攬特殊優秀人才補助, Ministry of Science and Technology, Taiwan
• 2020-2023, Career Development Award, National Health Research Institutes, Taiwan
• 2020-2022, Outstanding Young Scholar Research Grant , Ministry of Science and Technology, Taiwan
• 2020-2022, The Young Scholars' Creativity Award 傑出人才基金會年輕學者創新獎, The Foundation for the Advancement of Outstanding Scholarship, Taiwan
• 2012-current, member, RNA Society
• 2023, EMBO Global Investigator 歐洲分子生物學組織「全球研究學者」

1. Lin, C.-L.*, Taggart, A. J.*, Lim, K. H.*, Cygan, K. J., Ferraris, L., Creton, R., Huang, Y.-T., Fairbrother, W. G. (2016) RNA structure replaces the need for U2AF2 in splicing. Genome Research 26: 12-23. *equal contribution
2. Lin, C.-L., Taggart, A. J., Fairbrother, W. G. (2016) RNA structure in splicing: an evolutionary perspective. RNA Biol. 13: 766-771.
3. Taggart, A. J.*, Lin, C.-L.*, Shrestha, B., Heintzelman, C., Kim, S. W., Fairbrother, W. G. (2017) Large-scale analysis of branchpoint usage across species and cell lines. Genome Research 27: 639-649. *equal contribution
4. Soemedi, R., Cygan, K. J., Rhine, C., Glidden, D. T., Taggart, A. J., Lin, C.-L., Fredericks, A. M., Fairbrother, W. G. (2017) The effects of structure on pre-mRNA processing and stability. Methods 125: 36-44.
5. Kao, H.-J., Chiang, H.-L., Chen, H.-H., Fan, P.-C., Tu, Y.-F., Chou, Y.-Y., Hwu, W.-L., Lin, C.-L., Kwok, P.- Y., Lee, N.-C. (2020) De novo mutation and skewed X-inactivation in girl with BCAP31-related syndrome. Human Mutation 41: 1775-1782.
6. Chiang, H.-L.*, Chen, Y.-T.*, Su, J.-Y.*, Lin H.-N., Yu, A. C.-H., Hung, Y.-J., Wang, Y.-L., Huang, Y.-T., Lin, C.-L. (2022) Mechanism and modeling of human disease-associated near-exon intronic variants that perturb RNA splicing. Nature Structural & Molecular Biology 29: 1043–1055. *equal contribution