Bhattacharyya Suvendra N, Habermacher Regula, Martine Ursula, Closs Ellen I, Filipowicz Witold
Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, 4002 Basel, Switzerland.
Cell. 2006 Jun 16;125(6):1111-24. doi: 10.1016/j.cell.2006.04.031.
In metazoans, most microRNAs imperfectly base-pair with the 3' untranslated region (3'UTR) of target mRNAs and prevent protein accumulation by either repressing translation or inducing mRNA degradation. Examples of specific mRNAs undergoing microRNA-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 its 3'UTR can be relieved from the microRNA miR-122-induced inhibition in human hepatocarcinoma cells subjected to different stress conditions. The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies and its recruitment to polysomes. The derepression requires binding of HuR, an AU-rich-element binding 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.
在多细胞动物中，大多数微小RNA与靶标mRNA的3'非翻译区（3'UTR）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。经历微小RNA介导的抑制作用的特定mRNA的例子有很多，但这种抑制是否是一个可逆过程在很大程度上仍然未知。在这里，我们表明，在遭受不同应激条件的人肝癌细胞中，阳离子氨基酸转运体1（CAT-1）mRNA及其携带3'UTR的报告基因可以从微小RNA miR-122诱导的抑制中解除。CAT-1 mRNA的去抑制伴随着它从细胞质加工小体的释放及其向多核糖体的募集。这种去抑制需要富含AU元件结合蛋白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微小RNA抑制基因表达的潜力。
