한빛사논문, 상위피인용논문
Abstract
Toshiaki Shigeoka,1,4 Hosung Jung,2,4,5,* Jane Jung,2 Benita Turner-Bridger,1 Jiyeon Ohk,2 Julie Qiaojin Lin,1 Paul S. Amieux,3 and Christine E. Holt1,5,*
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
2Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
3Bastyr University Research Institute, Bastyr University, Kenmore, WA 98028, USA
4Co-first author
5Co-senior author
*Correspondence:Hosung Jung, Christine E. Holt
Summary
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.
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