A Novel Strategy for Regulating mRNA’s Degradation via Interfering the AUF1’s Binding to mRNA
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Published:2022-05-16
Issue:10
Volume:27
Page:3182
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Li Kun-Tao,Wu Xiong-Zhi,Sun Zhi-Yin,Ou Tian-Miao
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.
Funder
National Natural Science Foundation of China
Guangdong Provincial Science and Technology Development Special Foundation
Ministry of Education of China
Natural Science Foundation of Guangdong Province
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science