Department of Cellular and Molecular Medicine, University of California San Diego La Jolla, CA, USA.
Front Neurosci. 2012 Oct 2;6:144. doi: 10.3389/fnins.2012.00144. eCollection 2012.
Translational control of messenger RNAs (mRNAs) is a key aspect of neurobiology, defects of which can lead to neurological diseases. In response to stimuli, local translation of mRNAs is activated at synapses to facilitate long-lasting forms of synaptic plasticity, the cellular basis for learning, and memory formation. Translation, as well as all other aspects of RNA metabolism, is controlled in part by RNA binding proteins (RBPs) that directly interact with mRNAs to form mRNA-protein complexes. Disruption of RBP function is becoming widely recognized as a major cause of neurological diseases. Thus understanding the mechanisms that govern the interplay between translation control and RBP regulation in both normal and diseased neurons will provide new opportunities for novel diagnostics and therapeutic intervention. As a means of studying translational control, genome-wide methods are emerging as powerful tools that have already begun to unveil mechanisms that are missed by single-gene studies. Here, we describe the roles of RBPs in translational control, review genome-wide approaches to examine translational control, and discuss how the application of these approaches may provide mechanistic insight into the pathogenic underpinnings of RBPs in neurological diseases.
信使 RNA(mRNAs)的翻译调控是神经生物学的一个重要方面，其缺陷可导致神经退行性疾病。在受到刺激时，mRNA 在突触处的局部翻译被激活，以促进长时程突触可塑性，这是学习和记忆形成的细胞基础。翻译以及 RNA 代谢的所有其他方面都受到 RNA 结合蛋白(RBP)的控制，RBP 可直接与 mRNAs 相互作用形成 mRNA-蛋白复合物。RBP 功能的破坏正逐渐被广泛认为是神经退行性疾病的主要原因。因此，了解在正常和患病神经元中控制翻译调控与 RBP 调控之间相互作用的机制，将为新的诊断和治疗干预提供新的机会。作为研究翻译调控的一种手段，全基因组方法正在成为强大的工具，这些方法已经开始揭示单基因研究中遗漏的机制。在这里，我们描述了 RBP 在翻译调控中的作用，综述了全基因组方法来研究翻译调控，并讨论了这些方法的应用如何为神经退行性疾病中 RBP 的致病基础提供机制见解。
