Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
Open Biol. 2020 Sep;10(9):200177. doi: 10.1098/rsob.200177. Epub 2020 Sep 23.
Messenger RNA (mRNA) localization allows spatiotemporal regulation of the proteome at the subcellular level. This is observed in the axons of neurons, where mRNA localization is involved in regulating neuronal development and function by orchestrating rapid adaptive responses to extracellular cues and the maintenance of axonal homeostasis through local translation. Here, we provide an overview of the key findings that have broadened our knowledge regarding how specific mRNAs are trafficked and localize to axons. In particular, we review transcriptomic studies investigating mRNA content in axons and the molecular principles underpinning how these mRNAs arrived there, including cis-acting mRNA sequences and trans-acting proteins playing a role. Further, we discuss evidence that links defective axonal mRNA localization and pathological outcomes.
信使 RNA(mRNA)定位可在亚细胞水平上实现蛋白质组的时空调控。这种现象在神经元的轴突中观察到,mRNA 定位通过协调对细胞外信号的快速适应性反应以及通过局部翻译维持轴突稳态,参与调节神经元的发育和功能。在这里,我们提供了一个概述,介绍了哪些关键发现拓宽了我们对特定 mRNA 如何运输并定位于轴突的认识。特别是,我们回顾了研究轴突中 mRNA 含量的转录组学研究,以及这些 mRNA 到达轴突的分子原理,包括顺式作用的 mRNA 序列和发挥作用的反式作用蛋白。此外,我们还讨论了将轴突 mRNA 定位缺陷与病理结果联系起来的证据。