Researchers mapped the spatial translatomes of dorsal root ganglion neurons to uncover how individual axons establish distinct molecular identities, according to a study published in Nature Communications.
The team, led by Elizabeth S. Silagi and Rosalind A. Segal, used Translating Ribosome Affinity Purification and RNA sequencing, known as TRAP-seq. The technique revealed thousands of mRNAs preferentially translated within central axons, peripheral axons, or dorsal root ganglion cell bodies, termed somata. Many of these compartmentalized transcripts encode ion channels and neurotransmitter receptors. These localized products may confer unique electrophysiological and regenerative features to each axonal branch.
Integrating the TRAP-seq findings with published RNA-seq datasets revealed locally translated components that shift following neuropathic injury, indicating a route through which neurons alter local activity after nerve damage. The researchers uncovered specific RNA regulons governed by two RNA-binding proteins, SFPQ and SRSF10. SFPQ preferentially binds and transports mRNAs to peripheral axons, whereas SRSF10 directs mRNAs to central axons. This targeted sorting and translation process allows sensory neurons to dynamically modulate somatosensory function across distinct microenvironments.
Authors from the Department of Neurobiology at Harvard Medical School, the Dana-Farber Cancer Institute, and Brigham and Women’s Hospital contributed to the project. Michael Adkisson, Andrew Schroeder, Andrea Barczak, and Walter Eckalbar ran RNA sequencing at the University of California, San Francisco Genomics CoLab. RIP sequencing took place at Dana-Farber’s MBCF Genomics Core Facility under Zack Herbert and Maura Berkeley. The National Institutes of Health, the Rita Allen Foundation, and the Burroughs Wellcome Fund supported the work. Co-author William Renthal declared research support from Eli Lilly and company.
