Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.
BMB Rep. 2016 Apr;49(4):199-200. doi: 10.5483/bmbrep.2016.49.4.044.
Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. To systematically probe the changes in protein synthesis during memory formation, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database revealed novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without change in mRNA levels. At later time points, the expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls. [BMB Reports 2016; 49(4): 199-200].
脑内基因调控对于长期可塑性和记忆形成至关重要。尽管这一概念已经确立，但在记忆形成过程中，脑内的定量翻译图谱尚未被报道。为了系统地研究蛋白质合成在记忆形成过程中的变化，我们最近的研究利用核糖体谱分析技术，在学习事件发生后的多个时间点对小鼠海马组织进行了分析。对由此产生的数据库进行分析后发现，学习后存在新型的基因调控方式。首先，一组基因的翻译迅速受到抑制，而 mRNA 水平没有变化。在稍后的时间点，另一组基因的表达通过降低 mRNA 水平而下调。这种降低被预测是抑制 ESR1（雌激素受体 1）信号下游的结果。过表达翻译被抑制的基因之一 Nrsn1，或者通过注射激动剂激活 ESR1，会干扰记忆形成，这表明这些发现具有重要的功能意义。此外，在小鼠海马体中，除了其他基因外，编码翻译机制的基因的翻译也被发现受到抑制。总之，这种无偏倚的方法揭示了脑内基因调控的先前未被识别的特征，并强调了抑制控制的重要性。[BMB Reports 2016; 49(4): 199-200]。
