RBP-Driven RNA sorting and local translation establish the molecular identities of individual sensory axons

Neurons extend long axons that traverse distinct microenvironments, yet how these subcellular compartments acquire and maintain specialized identities remains unclear. Here, we use spatial translatomics to define the local translatomes of somatosensory dorsal root ganglion (DRG) neurons. Translating Ribosome Affinity Purification and RNA sequencing (TRAP-seq) reveal thousands of mRNAs preferentially translated within central axons, peripheral axons, or DRG somata, establishing compartment-specific translational programs. Many of these transcripts encode ion channels and neurotransmitter receptors that may confer distinct electrophysiological and regenerative properties to each axon. Integration of the TRAP-seq data with published RNA-seq identify locally translated components that change following neuropathic injury and could thereby adjust neuronal activity. We identify RNA regulons coordinated by RNA-binding proteins (RBPs) SFPQ and SRSF10, which preferentially bind and traffic mRNAs to peripheral or central axons, respectively. These findings indicate that RBP-guided RNA sorting and local translation enable the establishment and dynamic local modulation of somatosensory function.