应激诱导的人类细胞中微小RNA抑制作用的逆转及信使核糖核酸在加工小体中的定位

Stress-induced reversal of microRNA repression and mRNA P-body localization in human cells.

作者信息

Bhattacharyya S N, Habermacher R, Martine U, Closs E I, Filipowicz W

机构信息

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

出版信息

Cold Spring Harb Symp Quant Biol. 2006;71:513-21. doi: 10.1101/sqb.2006.71.038.

Abstract

In metazoa, microRNAs (miRNAs) imperfectly base-pair with the 3'-untranslated region (3'UTR) of mRNAs and prevent protein accumulation by either repressing translation or inducing mRNA degradation. Examples of specific mRNAs undergoing miRNA-mediated repression are numerous, but whether the repression is a reversible process remains largely unknown. Here, we show that cationic amino acid transporter 1 (CAT-1) mRNA and reporters bearing the CAT-1 3'UTR or its fragments can be relieved from the miRNA miR-122-induced inhibition in human hepatoma cells in response to different stress conditions. The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies (P bodies) and its recruitment to polysomes, indicating that P bodies act as storage sites for mRNAs inhibited by miRNAs. The derepression requires binding of HuR, an AU-rich-element-binding ELAV family protein, to the 3'UTR of CAT-1 mRNA. We propose that proteins interacting with the 3'UTR will generally act as modifiers altering the potential of miRNAs to repress gene expression.

摘要

在多细胞动物中,微小RNA(miRNA)与信使核糖核酸(mRNA)的3'非翻译区(3'UTR)进行不完全碱基配对,并通过抑制翻译或诱导mRNA降解来阻止蛋白质积累。经历miRNA介导的抑制作用的特定mRNA的例子众多,但这种抑制是否是一个可逆过程在很大程度上仍然未知。在此,我们表明,阳离子氨基酸转运体1(CAT-1)mRNA以及携带CAT-1 3'UTR或其片段的报告基因,在人肝癌细胞中,响应不同应激条件时,可从miR-122诱导的抑制中解除抑制。CAT-1 mRNA的去抑制伴随着其从细胞质加工小体(P小体)的释放以及其向多核糖体的募集,这表明P小体充当被miRNA抑制的mRNA的储存位点。这种去抑制需要富含AU元件结合的ELAV家族蛋白HuR与CAT-1 mRNA的3'UTR结合。我们提出与3'UTR相互作用的蛋白质通常会作为修饰因子改变miRNA抑制基因表达的潜力。

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