Abstract
Individual neurons have one or more axons that often extend long distances and traverse multiple microenvironments. However, it is not known how the composition of individual axons is established or locally modulated to enable neuronal function and plasticity. Here, we use spatial translatomics to identify local axonal translatomes in anatomically and functionally specialized neurons in the dorsal root ganglia (DRG). DRG neurons extend long central and peripheral axons in opposite directions and distinct microenvironments to enable somatosensation. Using Translating Ribosome Affinity Purification and RNA sequencing, we generated a comprehensive resource of mRNAs preferentially translated within each axon. Locally translated proteins include pain receptors, ion channels, and translational machinery, which establish distinct electrophysiologic properties and regenerative capacities for each axon. We identify RNA-binding proteins associated with sorting and transporting functionally related mRNAs. These findings provide resources for addressing how axonal translation shapes the spatial organization of neurons and enables subcellular neuroplasticity. HIGHLIGHTS: Distinct mRNAs are localized to and translated in individual axons.Axonal translatomes govern regenerative capacity, translational machinery, and electrophysiology.The RBP, SFPQ, coordinates mRNA sorting towards peripheral somatosensory axons.Axonal translatome data can be explored at painseq.shinyapps.io/CompartmentTRAP/.