【原】EIF4E1/4E-T复合体通过翻译抑制神经源性转录程序来决定前体神经元的发生

An eIF4E1/4E-T complex determines the genesis of neurons from precursors by translationally repressing a proneurogenic transcription program.

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|核心内容：

在这里，我们已经讨论了在发育过程中决定正确数量神经元发生的机制，重点放在胚胎皮质上。

我们在神经前体中发现了一个涉及eIF4E1及其结合伙伴4E-T的抑制复合体，它协同抑制决定神经发生的蛋白质的翻译。

这种eIF4E1/4E-T复合体与加工体蛋白Lsm1和Rck一起存在于P颗粒中，这种复合体的破坏会导致过早和增强的神经发生以及神经前体的枯竭。

对4E-T复合体的分析表明，它高度富含编码转录因子和分化相关蛋白的mRNAs。

其中包括神经源性的bHLH mRNAs，它与4E-T共定位在颗粒中，其蛋白产物在eIF4E、4E-T或加工体蛋白被敲除后异常上调。

因此，神经前体被转录启动以产生神经元，但eIF4E/4E-T复合体隔离并抑制神经源性蛋白的翻译，以确定适当的神经发生。

原文摘要：

Here, we have addressed the mechanisms that determine genesis of the correct numbers of neurons during development, focusing on the embryonic cortex. 

We identify in neural precursors a repressive complex involving eIF4E1 and its binding partner 4E-T that coordinately represses translation of proteins that determine neurogenesis. 

This eIF4E1/4E-T complex is present in granules with the processing body proteins Lsm1 and Rck, and disruption of this complex causes premature and enhanced neurogenesis and neural precursor depletion. 

Analysis of the 4E-T complex shows that it is highly enriched in mRNAs encoding transcription factors and differentiation-related proteins. These include the proneurogenic bHLH mRNAs, which colocalize with 4E-T in granules and whose protein products are aberrantly upregulated following knockdown of eIF4E, 4E-T, or processing body proteins. Thus, neural precursors are transcriptionally primed to generate neurons, but an eIF4E/4E-T complex sequesters and represses translation of proneurogenic proteins to determine appropriate neurogenesis.

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参考文献：https:///10.1016/j.neuron.2014.10.022

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