一种KH结构域RNA结合蛋白KSRP，通过招募降解机制促进富含AU元件（ARE）导向的mRNA周转。

A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery.

作者信息

Gherzi Roberto, Lee Kyung-Yeol, Briata Paola, Wegmüller Daniel, Moroni Christoph, Karin Michael, Chen Ching-Yi

机构信息

Gene Transfer Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genoa, Italy.

出版信息

Mol Cell. 2004 Jun 4;14(5):571-83. doi: 10.1016/j.molcel.2004.05.002.

DOI:10.1016/j.molcel.2004.05.002

PMID:15175153

Abstract

Inherently unstable mRNAs contain AU-rich elements (AREs) in their 3' untranslated regions that act as mRNA stability determinants by interacting with ARE binding proteins (ARE-BPs). The mechanisms underlying the function of ARE and ARE-BP interactions in promoting mRNA decay are not fully understood. Here, we demonstrate that KSRP, a KH domain-containing ARE-BP, is an essential factor for ARE-directed mRNA decay. Some of the KH motifs (KHs) of KSRP directly mediate RNA binding, mRNA decay, and interactions with the exosome and poly(A) ribonuclease (PARN). The ability of KHs to promote mRNA decay correlates with their ability to bind the ARE and associate with RNA-degrading enzymes. Thus, KHs promote rapid mRNA decay by recruiting degradation machinery to ARE-containing mRNAs.

摘要

内在不稳定的mRNA在其3'非翻译区含有富含AU的元件（AREs），这些元件通过与ARE结合蛋白（ARE-BPs）相互作用，作为mRNA稳定性的决定因素。ARE与ARE-BP相互作用促进mRNA降解的潜在机制尚未完全了解。在这里，我们证明了KSRP，一种含KH结构域的ARE-BP，是ARE介导的mRNA降解的关键因子。KSRP的一些KH基序（KHs）直接介导RNA结合、mRNA降解以及与外泌体和聚（A）核糖核酸酶（PARN）的相互作用。KHs促进mRNA降解的能力与其结合ARE和与RNA降解酶结合的能力相关。因此，KHs通过将降解机制招募到含ARE的mRNA上促进mRNA的快速降解。