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鹅去氧胆酸稳定 LDL 受体 mRNA 依赖于 3'-非翻译区和 AU 富含元件结合蛋白。

Chenodeoxycholic acid stabilization of LDL receptor mRNA depends on 3'-untranslated region and AU-rich element-binding protein.

机构信息

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.

出版信息

Biochem Biophys Res Commun. 2011 Jun 3;409(2):155-9. doi: 10.1016/j.bbrc.2011.04.006. Epub 2011 Apr 5.

DOI:10.1016/j.bbrc.2011.04.006
PMID:21473855
Abstract

Human low-density lipoprotein receptor (LDLR) mRNA is unstable and contains four AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). The aim of this study was to verify the involvement of the 3'-UTR in the rapid degradation of LDLR mRNA. This study revealed that the 3'-UTR is necessary and sufficient for the degradation, and that the 1st ARE (ARE1) close to the stop codon associates with cytoplasmic proteins, and is primarily responsible for the degradation. Chenodeoxycholic acid (CDCA) treatment stabilized chimeric GFP-LDLR 3'-UTR mRNA and accompanied mitogen-activated protein kinase (MAPK) activation. The UV cross-linking assays showed that a protein of 80kDa increasingly binds to the region including the ARE1 in response to CDCA-mediated MAPK activation.

摘要

人低密度脂蛋白受体(LDLR)mRNA 不稳定,在 3'-非翻译区(3'-UTR)中含有四个 AU 丰富元件(AREs)。本研究旨在验证 3'-UTR 是否参与 LDLR mRNA 的快速降解。本研究表明,3'-UTR 是降解所必需和充分的,并且靠近终止密码子的 1 号 ARE(ARE1)与细胞质蛋白结合,并主要负责降解。鹅去氧胆酸(CDCA)处理稳定嵌合 GFP-LDLR 3'-UTR mRNA,并伴随有丝分裂原激活蛋白激酶(MAPK)的激活。UV 交联实验表明,一种 80kDa 的蛋白随着 CDCA 介导的 MAPK 激活而越来越多地结合到包括 ARE1 在内的区域。

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