Regulation of ApC/EBP mRNA by the Aplysia AU‐rich element‐binding protein, ApELAV, and its effects on 5‐hydroxytryptamine‐induced long‐term facilitation-猫眼课题宝

海兔富含 AU 元素结合蛋白 ApELAV 对 ApC/EBP mRNA 的调节及其对 5-羟色胺诱导的长期促进的影响

DOI：

发表时间：

2006

期刊：

Journal of Neurochemistry

影响因子：

4.7

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Se;Yong;Jin;D. Chang;Jin;Hyoung F. Kim;Hyungju Park;H. Jun;V. N. Kim;B. Kaang

Aplysia CCAAT增强子结合蛋白(APC/EBP)是5-羟色胺(5-HT)诱导的海兔长期易化过程中的一个关键分子开关，在5-HT刺激下快速瞬时表达，但这种动态表达谱背后的机制尚不清楚。在这里，我们报告了APC/EBP在长期促进过程中的动态表达是由富含AU的元件(ARE)结合蛋白在转录后水平上调节的。我们发现APC/EBP mRNA的3‘UTR包含ARE的推测序列，ARE是一个典型的转录后顺式作用调控元件，调节不稳定mRNAs子集的稳定性和/或可译性。我们克隆了与ARE相关的RNA结合蛋白--海兔胚胎致死性异常视觉系统同源蛋白(ELAV/HU)，并阐明了该蛋白在APC/EBP基因表达调控中的作用。克隆的海兔胚胎致死性异常视觉系统(Aplysia ELAV/HU)蛋白，与APC/EBP基因3‘端非编码区内的AU富集区结合。此外，ApELAV还通过稳定增强因子调控APC/EBP3‘端非编码区报告基因的表达。尤其是当APC/EBP的3‘非编码区AU富集区过度表达时，5-羟色胺诱导的长期促进作用受到损害，这表明该区域在5-羟色胺诱导的APC/EBP表达以及由此导致的长期促进作用的形成中具有重要意义。我们的结果表明，Aplysia Are结合蛋白ApELAV可以在mRNA水平上调节APC/EBP基因的表达，因此，Are介导的转录后机制可能在调节APC/EBP对5-羟色胺刺激的反应中发挥关键作用。

Aplysia CCAAT enhancer‐binding protein (ApC/EBP), a key molecular switch in 5‐hydroxytryptamine (5‐HT)‐induced long‐term facilitation of Aplysia, is quickly and transiently expressed in response to a 5‐HT stimulus, but the mechanism underlying this dynamic expression profile remains obscure. Here, we report that the dynamic expression of ApC/EBP during long‐term facilitation is regulated at the post‐transcriptional level by AU‐rich element (ARE)‐binding proteins. We found that the 3′UTR of ApC/EBP mRNA contains putative sequences for ARE, which is a representative post‐transcriptional cis‐acting regulatory element that modulates the stability and/or the translatability of a distinct subset of labile mRNAs. We cloned the Aplysia homologue of embryonic lethal abnormal visual system homologue (ELAV/Hu) protein, one of the best‐studied RNA‐binding proteins that associate with ARE, and elucidated the involvement of Aplysia ELAV/Hu protein in ApC/EBP gene expressional regulation. Cloned Aplysia ELAV/Hu protein, Aplysia embryonic lethal abnormal visual system (ApELAV), bound to an AU‐rich region within the 3′UTR of ApC/EBP mRNA. Additionally, ApELAV controlled the expression of ApC/EBP 3′UTR‐containing reporter gene by functioning as a stability‐enhancing factor. In particular, 5‐HT‐induced long‐term facilitation was impaired when the AU‐rich region within the 3′UTR of ApC/EBP was over‐expressed, which suggests the significance of this region in 5‐HT‐induced ApC/EBP expression, and in the resultant formation of long‐term facilitation. Our results imply that the Aplysia ARE‐binding protein, ApELAV, can regulate ApC/EBP gene expression at the mRNA level, and accordingly, ARE‐mediated post‐transcriptional mechanism may serve a crucial function in regulating the expression of ApC/EBP in response to a 5‐HT stimulus.