1. A Novel Strategy for Regulating mRNA’s Degradation via Interfering the AUF1’s Binding to mRNA
- Author
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Kun-Tao Li, Xiong-Zhi Wu, Zhi-Yin Sun, and Tian-Miao Ou
- Subjects
AUF1 ,RNA-binding protein ,mRNA degradation ,gene transcription ,Organic chemistry ,QD241-441 - Abstract
The study on the mechanism and kinetics of mRNA degradation provides a new vision for chemical intervention on protein expression. The AU enrichment element (ARE) in mRNA 3′-UTR can be recognized and bound by the ARE binding protein (AU-rich Element factor (AUF1) to recruit RNase for degradation. In the present study, we proposed a novel strategy for expression regulation that interferes with the AUF1-RNA binding. A small-molecule compound, JNJ-7706621, was found to bind AUF1 protein and inhibit mRNA degradation by screening the commercial compound library. We discovered that JNJ-7706621 could inhibit the expression of AUF1 targeted gene IL8, an essential pro-inflammatory factor, by interfering with the mRNA homeostatic state. These studies provide innovative drug design strategies to regulate mRNA homeostasis.
- Published
- 2022
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