A Novel Strategy for Regulating mRNA’s Degradation via Interfering the AUF1’s Binding to mRNA

Autor: Kun-Tao Li, Xiong-Zhi Wu, Zhi-Yin Sun, Tian-Miao Ou
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecules, Vol 27, Iss 10, p 3182 (2022)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules27103182
Popis: 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.
Databáze: Directory of Open Access Journals