Analgesic targets identified in mouse sensory neuron somata and terminal pain translatomes
M. Ali Bangash,
Cankut Cubuk,
Federico Iseppon,
Rayan Haroun,
Chloe Garcia,
Ana P. Luiz,
Manuel Arcangeletti,
Samuel J. Gossage,
Sonia Santana-Varela,
James J. Cox,
Myles J. Lewis,
John N. Wood,
Jing Zhao
Affiliations
M. Ali Bangash
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Cankut Cubuk
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
Federico Iseppon
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Rayan Haroun
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Chloe Garcia
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Ana P. Luiz
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Manuel Arcangeletti
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Samuel J. Gossage
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Sonia Santana-Varela
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
James J. Cox
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK
Myles J. Lewis
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
John N. Wood
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK; Corresponding author
Jing Zhao
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London WC1E 6BT, UK; Corresponding author
Summary: 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.
