Abstract
SummaryLocal 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.
Highlights
RNA localization and local translation are evolutionarily conserved mechanisms employed by cells to control the precise subcellular positioning of nascent proteins
We found that synapse- and axon-related gene ontology (GO) terms were generally associated with the axonal translatome, whereas the retina-only translatome was enriched with basal body and nuclear GO terms (Figure 3C)
Targets of mammalian target of rapamycin complex 1 (mTORC1), fragile X mental retardation protein (FMRP), and adenomatous polyposis coli (APC) Show Translational Co-regulation in a Stage-Specific Manner We have shown that the axonal translatome is dynamically regulated during development, and this raises the important question of how axonal translation is controlled by upstream signaling pathways
Summary
Local mRNA translation in axons of developing and adult CNS neurons in vivo shows dynamic regulation, suggesting functional relevance for neural circuit formation and maintenance. Highlights d Dynamic translatome of retinal axons in vivo matches changing subcellular function. 2016, Cell 166, 181–192 June 30, 2016 a 2016 The Author(s).
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