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Identification of an RNA-binding perturbing characteristic for thiopurine drugs and their derivatives to disrupt CELF1–RNA interaction

Nucleic Acids Research. 2024-09; 
Yang Tan , Zhibo Zhao , Qingfang Han , Peipei Xu , Xiaopeng Shen , Yajun Jiang , Qiang Xu , Xingxin Wu
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Plasmid DNA Preparation The plasmid pcDNA3.1-NLS-MCP-VenusN, pcDNA3.1- NES-HA-VenusC, pcDNA3.1-GST-stop codon-12 × MS2, pcDNA3.1-GST-stop codon-12 × MS2-EDEN(2U/4U) were synthesized by GenScript. Get A Quote

摘要

RNA-binding proteins (RBPs) are attractive targets in human pathologies. Despite a number of efforts to target RBPs with small molecules, it is still difficult to develop RBP inhibitors, asking for a deeper understanding of how to chemically perturb RNA-binding activity. In this study, we found that the thiopurine drugs (6-mercaptopurine and 6-thioguanine) effectively disrupt CELF1-RNA interaction. The disrupting activity relies on the formation of disulfide bonds between the thiopurine drugs and CELF1. Mutating the cysteine residue proximal to the RNA recognition motifs (RRMs), or adding reducing agents, abolishes the disrupting activity. Furthermore, the 1,2,4-triazole-3-thione, a thiopurine analogue, was ide... More

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