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A Novel Strategy for Regulating mRNA's Degradation via Interfering the AUF1's Binding to mRNA.
Li, Kun-Tao; Wu, Xiong-Zhi; Sun, Zhi-Yin; Ou, Tian-Miao.
Afiliación
  • Li KT; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • Wu XZ; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • Sun ZY; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • Ou TM; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Molecules ; 27(10)2022 May 16.
Article en En | MEDLINE | ID: mdl-35630659
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteína Heterogénea-Nuclear Grupo D Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteína Heterogénea-Nuclear Grupo D Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza