Grosset Christophe, Boniface Rachel, Duchez Pascale, Solanilla Anne, Cosson Bertrand, Ripoche Jean
FRE 2617 CNRS, Université Victor Ségalen Bordeaux 2, 33076 Bordeaux, France.
J Biol Chem. 2004 Apr 2;279(14):13354-62. doi: 10.1074/jbc.M308003200. Epub 2004 Jan 15.
The AU-rich element (ARE) controls the turnover of many unstable mRNAs and their translation. The granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE is known to be a destabilizing element, but its role in translation remains unclear. Here we studied in vivo the role of the GM-CSF ARE on the mRNA and protein expressions of an enhanced green fluorescent protein reporter gene. The GM-CSF ARE had a repressor effect on translation independently of its effect on mRNA levels. In the context of an internal ribosome entry site, the GM-CSF ARE still repressed translation but was no longer functional as a destabilizing element. Gel retardation assays showed that poly(A)-binding protein is displaced from the poly(A) tail when the ARE is present in the 3'-untranslated region. These data suggest that the GM-CSF ARE controls translation and mRNA decay by interfering with poly(A)-binding protein-mediated mRNA circularization.
富含AU元件（ARE）控制着许多不稳定mRNA的周转及其翻译。已知粒细胞-巨噬细胞集落刺激因子（GM-CSF）的ARE是一种使mRNA不稳定的元件，但其在翻译中的作用仍不清楚。在此，我们在体内研究了GM-CSF的ARE对增强型绿色荧光蛋白报告基因的mRNA和蛋白质表达的作用。GM-CSF的ARE对翻译具有抑制作用，且与其对mRNA水平的影响无关。在内部核糖体进入位点的情况下，GM-CSF的ARE仍能抑制翻译，但不再作为使mRNA不稳定的元件发挥作用。凝胶阻滞分析表明，当ARE存在于3'非翻译区时，多聚腺苷酸结合蛋白会从多聚腺苷酸尾部分离。这些数据表明，GM-CSF的ARE通过干扰多聚腺苷酸结合蛋白介导的mRNA环化来控制翻译和mRNA降解。
