Posttranscriptional regulation of the immediate-early gene EGR1 by light in the mouse retina.
Posttranscriptional regulation of the immediate-early gene EGR1 by light in the mouse retina.
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小鼠视网膜中光对立即早期基因 EGR1 的转录后调节。
DOI：
10.1111/j.1460-9568.2004.03811.x
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Schaeffel,Frank
中科院分区：
文献类型：
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作者：
Simon,Perikles;Schott,Klaus;Williams,RobertW;Schaeffel,Frank
突触可塑性是由转录因子的差异调控调节的，如通过锌指结合域与DNA结合的asegr1。fegr1的失活暗示该基因是记忆形成和学习的关键调节因子。然而，突触输入如何在短短几分钟内导致EGR - 1蛋白的上调仍然令人困惑。在这里，我们通过免疫组织化学染色显示EGR - 1蛋白定位于整个小鼠视网膜的突触中。我们首次证明fegr‐1mRNA的两个变体在视网膜中通过选择性聚腺苷化产生，较长的版本在3'UTR末端有额外的293个碱基对。值得注意的是，替代聚腺苷化位点的使用是由光控制的。较长变异的额外3'UTR序列比这个高度保守的基因的编码区域显示出更高的系统发育保守性。此外，它还含有胞质聚腺苷化元件，已知该元件对NMDA受体激活有反应。因此，egr‐1mRNA的较长版本可以快速响应兴奋性刺激，如光或谷氨酸释放，而主要表达并包含完整编码序列的较短版本在其3'UTR中缺乏细胞质聚腺苷化的调节元件。
Synaptic plasticity is modulated by differential regulation of transcription factors such asEGR1which binds to DNA via a zinc finger binding domain. Inactivation ofEGR1has implicated this gene as a key regulator of memory formation and learning. However, it remains puzzling how synaptic input can lead to an up‐regulation of the EGR‐1 protein within only a few minutes. Here, we show by immunohistochemical staining that the EGR‐1 protein is localized in synapses throughout the mouse retina. We demonstrate for the first time that two variants ofEgr‐1mRNA are produced in the retina by alternative polyadenylation, with the longer version having an additional 293 base pairs at the end of the 3′UTR. Remarkably, the use of the alternative polyadenylation site is controlled by light. The additional 3′UTR sequence of the longer variant displays an even higher level of phylogenetic conservation than the coding region of this highly conserved gene. Additionally, it harbours a cytoplasmic polyadenylation element which is known to respond to NMDA receptor activation. The longer version of theEgr‐1mRNA could therefore rapidly respond to excitatory stimuli such as light or glutamate release whereas the short variant, which is predominantly expressed and contains the full coding sequence, lacks the regulatory elements for cytoplasmic polyadenylation in its 3′UTR.