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Updated: Jan 17, 2026

Extremely Rapid and Specific Metabolic Labelling of RNA In Vivo with 4-Thiouracil Ers4tU
Published on: August 22, 2019
Nature-Inspired Chemical Probes for Labeling tRNAs Containing 2-Thiouridine (s2U)
Hongling Zhou1,2, Yuanyuan Li1, Jingwen Zhang1
1Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Abstract:
RNA modifications play pivotal roles in numerous cellular processes and human diseases. In addition to the well-studied methyl-based modifications, hydrophobic prenyl-modifications have also been found in many RNA species. Herein, a chemical labeling strategy for tagging specific tRNAs by taking advantage of a natural SelU-mediated geranylation process is reported. A series of "clickable" geranyl-pyrophosphate analogs is synthesized and two candidates to label 2-thiouridine (s2U) containing tRNA using a two-step process, azidation-and-click-tagging with fluorescent dyes, namely ACT-Flu are identified. This method has also been applied to in-cell RNA imaging, providing a useful biochemical toolset to further study the biological functions of s2U-tRNAs and monitor their status in both healthy and diseased cells, since human tRNAs do not have the prenyl group on natural s2U34 modification.
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