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Discovery of A G-Quadruplex Unwinder That Unleashes the Translation of G-Quadruplex-Containing mRNA without Inducing DNA Damage

文献类型：期刊论文

作者Teng, Xucong2,3,4,5; Hu, Difei2; Dai, Yicong2; Jing, Haitao1; Hu, Wenxuan1; Zhang, Qiushuang2; Zhang, Na1; Li, Jinghong2,3,4,5
刊名ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
出版日期2024-08-16
关键词G-quadruplex unwinder DNA damage translation chemical targeting
ISSN号1433-7851
DOI10.1002/anie.202407353
通讯作者Li, Jinghong(jhli@mail.tsinghua.edu.cn)
英文摘要To explore the mechanisms and therapeutic strategies for G-quadruplex (G4) mediated diseases, it is crucial to manipulate and intervene in intracellular G4 structures using small molecular tools. While hundreds of G4 stabilizers have been developed, there is a significant gap in the availability of G4 unwinding agents. Here, we propose a strategy to disrupt G-quadruplexes by forming G-C hydrogen bonds with chemically modified cytidine trimers. We validated a good G4 unwinder, the 2 '-F cytidine trimer (2 '-F C3). 2 '-F C3 does not inhibit cell growth nor cause severe DNA damage at a concentration below 10 mu M. Moreover, 2 '-F C3 does not affect gene transcription nor RNA splicing, while it significantly enhances the translation of G4-containing mRNA and upregulates RNA splicing, RNA processing and cell cycle pathways. The discovery of this G4 unwinder provides a functional tool for the chemical modulation of G4s in living cells. We discovered a G4 unwinder, 2 '-F C3, capable of promoting the unwinding of both DNA and RNA G4 structures. In living cells, 2 '-F C3 does not induce severe DNA damage at a concentration below 10 mu M, nor does it broadly interfere with G4-related biological processes. Specially, it can enhance the translation level of G4-containing mRNA. image
WOS关键词SMALL-MOLECULE ; GENE-EXPRESSION ; TRANSCRIPTION ; DESTABILIZES ; CX-5461 ; CELLS
资助项目National Natural Science Foundation of China[22034004] ; National Natural Science Foundation of China[22027807] ; National Key Research and Development Program of China[2021YFA1200104] ; New Cornerstone Science Foundation, China Postdoctoral Science Foundation[2023M731972] ; New Cornerstone Science Foundation, China Postdoctoral Science Foundation[BX20230179] ; Beijing Life Science Academy Initiative Scientific Research Program[2023000CA0050] ; Beijing Life Science Academy Initiative Scientific Research Program[2023100CC0240] ; Beijing Life Science Academy Initiative Scientific Research Program[2023100CC0250]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001291382400001
出版者WILEY-V C H VERLAG GMBH
资助机构National Natural Science Foundation of China ; National Key Research and Development Program of China ; New Cornerstone Science Foundation, China Postdoctoral Science Foundation ; Beijing Life Science Academy Initiative Scientific Research Program
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/135970]  
专题中国科学院合肥物质科学研究院
通讯作者Li, Jinghong
作者单位1.Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Hefei 230031, Peoples R China
2.Tsinghua Univ, Dept Chem, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Beijing 100084, Peoples R China
3.New Cornerstone Sci Lab, Shenzhen 518054, Peoples R China
4.Beijing Life Sci Acad, Beijing 102209, Peoples R China
5.Univ Sci & Technol China, Ctr BioAnalyt Chem, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Peoples R China
推荐引用方式
GB/T 7714		 Teng, Xucong,Hu, Difei,Dai, Yicong,et al. Discovery of A G-Quadruplex Unwinder That Unleashes the Translation of G-Quadruplex-Containing mRNA without Inducing DNA Damage[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2024.
APA Teng, Xucong.,Hu, Difei.,Dai, Yicong.,Jing, Haitao.,Hu, Wenxuan.,...&Li, Jinghong.(2024).Discovery of A G-Quadruplex Unwinder That Unleashes the Translation of G-Quadruplex-Containing mRNA without Inducing DNA Damage.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION.
MLA Teng, Xucong,et al."Discovery of A G-Quadruplex Unwinder That Unleashes the Translation of G-Quadruplex-Containing mRNA without Inducing DNA Damage".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2024).

入库方式： OAI收割

来源：合肥物质科学研究院

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