Shigeoka Toshiaki, Jung Hosung, Jung Jane, Turner-Bridger Benita, Ohk Jiyeon, Lin Julie Qiaojin, Amieux Paul S, Holt Christine E
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Cell. 2016 Jun 30;166(1):181-92. doi: 10.1016/j.cell.2016.05.029. Epub 2016 Jun 16.
Local mRNA translation mediates the adaptive responses of axons to extrinsic signals, but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles, suggesting distinct steps in axon wiring, such as elongation, pruning, and synaptogenesis. Adult axons, remarkably, have a complex translatome with strong links to axon survival, neurotransmission, and neurodegenerative disease. Translationally co-regulated mRNA subsets share common upstream regulators, and sequence elements generated by alternative splicing promote axonal mRNA translation. Our results indicate that intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo.
局部mRNA翻译介导轴突对外源信号的适应性反应，但在体内哺乳动物中枢神经系统轴突中发生这种现象的直接证据却很少。我们在小鼠中开发了一种轴突捕获-核糖体标签方法，该方法允许对体内发育中和成年视网膜-脑顶盖投射的视网膜神经节细胞轴突中与核糖体结合的mRNA进行深度测序分析。从胚胎到出生后的轴突翻译组包含一个不断演变的、具有轴突特异性作用的富集基因子集，这表明轴突布线过程中存在不同步骤，如伸长、修剪和突触形成。值得注意的是，成年轴突具有一个复杂的翻译组，与轴突存活、神经传递和神经退行性疾病密切相关。翻译共调控的mRNA子集共享共同的上游调节因子，并且由可变剪接产生的序列元件促进轴突mRNA翻译。我们的结果表明，哺乳动物中枢神经系统轴突中特定区域mRNA翻译的复杂调控支持了体内神经回路的形成和维持。
