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

被引:117
作者
Bhattacharyya, S. N. [1 ]
Habermacher, R.
Martine, U.
Closs, E. I.
Filipowicz, W.
机构
[1] Friedrich Miescher Inst Biomed Res, CH-4002 Basel, Switzerland
[2] Johannes Gutenberg Univ Mainz, Dept Pharmacol, D-55101 Mainz, Germany
关键词
D O I
10.1101/sqb.2006.71.038
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 hearing 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 miRNA;. 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.
引用
收藏
页码:513 / 521
页数:9
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