Iijima Takatoshi, Hidaka Chiharu, Iijima Yoko
Tokai University Institute of Innovative Science and Technology, 143 Shimokasuya, Isehara City, Kanagawa 259-1193, Japan; Tokai University Institute of Innovative Science and Technology, 4-1-1 Kitakaname, Hiratsuka City, Kanagawa 259-1292, Japan; School of Medicine, Tokai University, 143 Shimokasuya, Isehara City, Kanagawa 259-1193, Japan.
Tokai University Institute of Innovative Science and Technology, 143 Shimokasuya, Isehara City, Kanagawa 259-1193, Japan; Tokai University Institute of Innovative Science and Technology, 4-1-1 Kitakaname, Hiratsuka City, Kanagawa 259-1292, Japan; School of Medicine, Tokai University, 143 Shimokasuya, Isehara City, Kanagawa 259-1193, Japan.
Neurosci Res. 2016 Aug;109:1-8. doi: 10.1016/j.neures.2016.01.010. Epub 2016 Feb 4.
Alternative pre-mRNA splicing is a fundamental mechanism that generates molecular diversity from a single gene. In the central nervous system (CNS), key neural developmental steps are thought to be controlled by alternative splicing decisions, including the molecular diversity underlying synaptic wiring, plasticity, and remodeling. Significant progress has been made in understanding the molecular mechanisms and functions of alternative pre-mRNA splicing in neurons through studies in invertebrate systems; however, recent studies have begun to uncover the potential role of neuronal alternative splicing in the mammalian CNS. This article provides an overview of recent findings regarding the regulation and function of neuronal alternative splicing. In particular, we focus on the spatio-temporal regulation of neurexin, a synaptic adhesion molecule, by neuronal cell type-specific factors and neuronal activity, which are thought to be especially important for characterizing neural development and function within the mammalian CNS. Notably, there is increasing evidence that implicates the dysregulation of neuronal splicing events in several neurological disorders. Therefore, understanding the detailed mechanisms of neuronal alternative splicing in the mammalian CNS may provide plausible treatment strategies for these diseases.
可变前体mRNA剪接是一种从单个基因产生分子多样性的基本机制。在中枢神经系统(CNS)中,关键的神经发育步骤被认为受可变剪接决定的控制,包括突触连接、可塑性和重塑背后的分子多样性。通过对无脊椎动物系统的研究,在理解神经元中可变前体mRNA剪接的分子机制和功能方面取得了重大进展;然而,最近的研究开始揭示神经元可变剪接在哺乳动物中枢神经系统中的潜在作用。本文概述了有关神经元可变剪接调控和功能的最新发现。特别是,我们关注神经细胞粘附分子神经连接蛋白由神经元细胞类型特异性因子和神经元活动进行的时空调控,这被认为对表征哺乳动物中枢神经系统内的神经发育和功能尤为重要。值得注意的是,越来越多的证据表明神经元剪接事件的失调与几种神经疾病有关。因此,了解哺乳动物中枢神经系统中神经元可变剪接的详细机制可能为这些疾病提供合理的治疗策略。