The ELAV Protein HuD Stimulates Cap-Dependent Translation in a Poly(A)- and eIF4A-Dependent Manner
The ELAV Protein HuD Stimulates Cap-Dependent Translation in a Poly(A)- and eIF4A-Dependent Manner
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DOI：
10.1016/j.molcel.2009.11.013
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发表时间：
2009-12-24
期刊：
影响因子：
16
通讯作者：
Fujiwara, Toshinobu
中科院分区：
文献类型：
--
作者：
Fukao, Akira;Sasano, Yumi;Fujiwara, Toshinobu
RNA结合蛋白HuD通过未知的机制促进神经元分化。在这里，我们确定了HuD在翻译中的增强子功能。HuD的翻译刺激需要3' poly（A）尾和5' m（7）G帽结构。我们还表明，HuD直接与eIF 4A相互作用。HuD的这种相互作用和poly（A）结合活性对其翻译增强子功能至关重要，因为HuD-eIF 4A-和HuD-poly（A）结合突变体不能刺激翻译。我们表明，HCV IRES mRNA的翻译，这是eIF 4A的独立，是不是由HuD刺激。我们还发现HuD的eIF 4A和poly（A）结合活性不仅对刺激翻译很重要，而且对HuD诱导的PC 12细胞神经突生长也很重要。这个帽依赖性翻译调控的例子可能至少部分解释HuD如何触发神经元分化的诱导。
The RNA-binding protein HuD promotes neuronal differentiation by an unknown mechanism. Here we identify an enhancer function of HuD in translation. Translation stimulation by HuD requires both a 3' poly(A) tail and a 5' m(7)G cap structure. We also show that HuD directly interacts with eIF4A. This interaction and the poly(A)-binding activity of HuD are critical for its translational enhancer function because HuD-eIF4A- and HuD-poly(A)-binding mutants fail to stimulate translation. We show that translation of HCV IRES mRNA, which is eIF4A independent, is not stimulated by HuD. We also find that the eIF4A and poly(A)-binding activities of HuD are not only important for stimulating translation but also are essential for HuD-induced neurite outgrowth in PC12 cells. This example of cap-dependent translational regulation might explain at least in part how HuD triggers the induction of neuronal differentiation.