McMahon J J, Miller E E, Silver D L
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, United States.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, United States; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, United States; Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC 27710, United States.
Int J Dev Neurosci. 2016 Dec;55:117-123. doi: 10.1016/j.ijdevneu.2016.03.006. Epub 2016 Apr 9.
Post-transcriptional mRNA metabolism has emerged as a critical regulatory nexus in proper development and function of the nervous system. In particular, recent studies highlight roles for the exon junction complex (EJC) in neurodevelopment. The EJC is an RNA binding complex composed of 3 core proteins, EIF4A3 (DDX48), RBM8A (Y14), and MAGOH, and is a major hub of post-transcriptional regulation. Following deposition onto mRNA, the EJC serves as a platform for the binding of peripheral factors which together regulate splicing, nonsense mediated decay, translation, and RNA localization. While fundamental molecular roles of the EJC have been well established, the in vivo relevance in mammals has only recently been examined. New genetic models and cellular assays have revealed core and peripheral EJC components play critical roles in brain development, stem cell function, neuronal outgrowth, and neuronal activity. Moreover, human genetics studies increasingly implicate EJC components in the etiology of neurodevelopmental disorders. Collectively, these findings indicate that proper dosage of EJC components is necessary for diverse aspects of neuronal development and function. Going forward, genetic models of EJC components will provide valuable tools for further elucidating functions in the nervous system relevant for neurodevelopmental disease.
转录后mRNA代谢已成为神经系统正常发育和功能的关键调控枢纽。特别是，最近的研究突出了外显子连接复合体（EJC）在神经发育中的作用。EJC是一种由3种核心蛋白EIF4A3（DDX48）、RBM8A（Y14）和MAGOH组成的RNA结合复合体，是转录后调控的主要中心。在沉积到mRNA上后，EJC作为外周因子结合的平台，这些外周因子共同调节剪接、无义介导的衰变、翻译和RNA定位。虽然EJC的基本分子作用已经得到充分确立，但在哺乳动物体内的相关性直到最近才被研究。新的遗传模型和细胞分析表明，EJC的核心和外周成分在大脑发育、干细胞功能、神经元生长和神经元活动中发挥着关键作用。此外，人类遗传学研究越来越多地表明EJC成分与神经发育障碍的病因有关。总的来说，这些发现表明，EJC成分的适当剂量对于神经元发育和功能的各个方面都是必要的。展望未来，EJC成分的遗传模型将为进一步阐明与神经发育疾病相关的神经系统功能提供有价值的工具。
