Analgesic targets identified in mouse sensory neuron somata and terminal pain translatomes
The relationship between transcription and protein expression is complex. We identified polysome-associated RNA transcripts in the somata and central terminals of mouse sensory neurons in control, painful (plus nerve growth factor), and pain-free conditions (Nav1.7-null mice). The majority (98%) of translated transcripts are shared between male and female mice in both the somata and terminals. Some transcripts are highly enriched in the somata or terminals. Changes in the translatome in painful and pain-free conditions include novel and known regulators of pain pathways. Antisense knockdown of selected somatic and terminal polysome-associated transcripts that correlate with pain states diminished pain behavior. Terminal-enriched transcripts included those encoding synaptic proteins (e.g., synaptotagmin), non-coding RNAs, transcription factors (e.g., Znf431), proteins associated with transsynaptic trafficking (HoxC9), GABA-generating enzymes (Gad1 and Gad2), and neuropeptides (Penk). Thus, central terminal translation may well be a significant regulatory locus for peripheral input from sensory neurons.
Authors
- Rayan Haroun
- James J. Cox (ORCID: https://orcid.org/0000-0002-9129-8011)
- Jing Zhao (ORCID: https://orcid.org/0000-0003-2587-1198)
- Samuel J. Gossage (ORCID: https://orcid.org/0009-0005-6020-5029)
- John N. Wood (ORCID: https://orcid.org/0000-0002-9166-8158)
- Myles Lewis (ORCID: https://orcid.org/0000-0001-9365-5345)
- Sonia Santana‐Varela (ORCID: https://orcid.org/0000-0002-6063-8669)
- Ana Paula Luiz (ORCID: https://orcid.org/0000-0002-9465-0797)
- Federico Iseppon (ORCID: https://orcid.org/0000-0002-1981-1204)
- Manuel Arcangeletti
- Cankut Çubuk (ORCID: https://orcid.org/0000-0003-4646-0849)
- Muhammad Bangash (ORCID: https://orcid.org/0000-0003-1696-2792)
- G Chloé
Institutions
- Queen Mary University of London (GB)
- William Harvey Research Institute (GB)
- Institute of Structural and Molecular Biology (GB)
- University College London (GB)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-08-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114614
- Citations
- 4
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.31
Funders
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- Cancer Research UK
- National Institute for Health and Care Research
- Versus Arthritis
- Medical Research Council
- Cancer Research UK Cambridge Institute, University of Cambridge