Dynamic association with polysomes during P19 neuronal differentiation and an untranslated-region-dependent translation regulation of the tau mRNA by the tau mRNA-Associated proteins IMP1, HuD, and G3BP1
Dynamic association with polysomes during P19 neuronal differentiation and an untranslated-region-dependent translation regulation of the tau mRNA by the tau mRNA-Associated proteins IMP1, HuD, and G3BP1
复制标题
DOI：
10.1002/jnr.21099
复制
发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Ginzburg, Irith
中科院分区：
文献类型：
--
作者：
Atlas, Roee;Behar, Leah;Ginzburg, Irith
mRNA翻译的调节是在分化过程中介导神经元极性的关键步骤，因为神经元极性部分地由树突和轴突发出时特定mRNA分子的局部翻译决定。神经元中mRNA结合蛋白的多样性在控制mRNA翻译中起着重要作用。这些蛋白质与核糖体和翻译因子相关，从而在时间和空间上调节翻译过程。在先前的研究中，我们已经显示了tau mRNA结合蛋白HuD、IMP 1和G3 BP 1与P19神经元中的翻译多核糖体之间的关联。在本研究中，我们通过P19神经元分化以及这些蛋白质对tau mRNA翻译的功能影响，确定了G3 BP 1，IMP 1和HuD与多聚核糖体之间的关联动力学。我们显示了一种新的，分化依赖的协会，这些蛋白质与多聚核糖体。此外，我们还发现IMP 1、G3 BP 1和HuD蛋白在HEK-293细胞中对tau mRNA的翻译有强烈的负面影响。据我们所知，这是G3 BP 1对任何mRNA的直接翻译作用的首次观察，也是IMP 1和HuD对细胞系统中tau mRNA的翻译抑制的首次报道。翻译抑制被证明是由tau mRNA 3'非翻译区（UTR）介导的，从而为这些序列提供了新的翻译作用，这些序列先前与mRNA稳定有关。我们还定义了一种新的机制IMP 1结合tau mRNA，这表明构象结合，这是不依赖于序列。(c)2006威利-利斯公司
Regulation of mRNA translation is a key step in mediating neuronal polarity during differentiation, insofar as neuronal polarity is partially determined by local translation of specific mRNA molecules as dendrites and axons are emanating. The multiplicity of mRNA-binding proteins in neurons plays an essential role in controlling mRNA translation. These proteins are associated with ribosomes and translation factors, thereby regulating both temporally and spatially the translation process. In a previous study, we have shown an association among the tau mRNA-binding proteins HuD, IMP1, and G3BP1 with translating polysomes in P19 neurons. In the present study, we determined the dynamics of the association among G3BP1, IMP1, and HuD with polysomes through P19 neuronal differentiation as well as the functional effect of these proteins on tau mRNA translation. We show a novel, differentiation-dependent association of these proteins with polysomes. In addition, we show a strong, negative effect on translation of the tau mRNA by IMP1, G3BP1, and HuD proteins in HEK-293 cells. To our knowledge this is the first observation of a direct translational role of G3BP1 for any mRNA and the first report of a translation inhibition by IMP1 and HuD on the tau mRNA in a cell system. The translation inhibition is shown to be mediated by the tau mRNA 3' untranslated regions (UTRs), thus giving a new, translational role for these sequences, which were previously implicated in mRNA stabilization. We also define a novel mechanism for IMP1 binding to tau mRNA, which suggests a conformational binding, which is not sequence dependent. (c) 2006 Wiley-Liss, Inc.