Comprehensive analysis of long noncoding RNA expression in dorsal root ganglion reveals cell-type specificity and dysregulation after nerve injury.

Georgios Baskozos,Alex J Clark,Christine Orengo,Jeffrey S Mogil,David L Bennett,Teodora Trendafilova,Jean S Austin,Jon G Lees,Lucy Mcdermott,John M Dawes,Ana Antunes-Martins,Stephen B Mcmahon

doi:10.1097/j.pain.0000000000001416

Abstract

Dorsal root ganglion (DRG) neurons provide connectivity between peripheral tissues and the spinal cord. Transcriptional plasticity within DRG sensory neurons after peripheral nerve injury contributes to nerve repair but also leads to maladaptive plasticity, including the development of neuropathic pain. This study presents tissue and neuron-specific expression profiling of both known and novel long noncoding RNAs (LncRNAs) in the rodent DRG after nerve injury. We have identified a large number of novel LncRNAs expressed within the rodent DRG, a minority of which were syntenically conserved between the mouse, rat, and human, and including, both intergenic and antisense LncRNAs. We have also identified neuron type-specific LncRNAs in the mouse DRG and LncRNAs that are expressed in human IPS cell-derived sensory neurons. We show significant plasticity in LncRNA expression after nerve injury, which in mice is strain and gender dependent. This resource is publicly available and will aid future studies of DRG neuron identity and the transcriptional landscape in both the naive and injured DRG. We present our work regarding novel antisense and intergenic LncRNAs as an online searchable database, accessible from PainNetworks (http://www.painnetworks.org/). We have also integrated all annotated gene expression data in PainNetworks, so they can be examined in the context of their protein interactions.

Highlights

Dorsal root ganglion (DRG) neurons provide connectivity between peripheral targets and the spinal cord
To identify unknown transcribed regions outside known gene models and group them into transcriptional units representing putative novel long noncoding RNAs (LncRNAs) on the gene level, we performed RNA-sequencing (RNA-Seq) of DRG tissue harvested from animal models of nerve injury vs sham controls
To identify nonannotated I.o.E and to differentiate them from untranslated regions (UTRs) or not-yet-annotated exons belonging to known gene models, we filtered out reads overlapping ENSEMBL and RefSeq annotations as well as genomic regions of 1000 bp from the 59 and 39 end of known gene models

Summary

Introduction

Dorsal root ganglion (DRG) neurons provide connectivity between peripheral targets and the spinal cord. These neurons show significant heterogeneity in relation to their morphology, functional properties, growth factor dependence, and transcriptional. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. A Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom, Departments of b Psychology and, c Anesthesia, Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada, d Neurorestoration Group, Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom, e Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom

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