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RNA isoform expression landscape of the human dorsal root ganglion generated from long-read sequencing
Open accessPublished version of a preprint
Abstract
Splicing is a posttranscriptional RNA processing mechanism that enhances genomic complexity by creating multiple isoforms from the same gene. We aimed to characterize the isoforms expressed in the human peripheral nervous system, with the goal of creating a resource to identify novel isoforms of functionally relevant genes associated with somatosensation and nociception. We used long-read sequencing to document isoform expression in the human dorsal root ganglia from 3 organ donors and validated in silico by confirming expression in short-read sequencing from 3 independent organ donors. Nineteen thousand five hundred forty-seven isoforms of protein-coding genes were detected and validated. We identified 763 isoforms with at least one previously undescribed splice junction. Previously unannotated isoforms of multiple pain-associated genes, including ASIC3 , MRGPRX1 , and HNRNPK , were identified. In the novel isoforms of ASIC3 , a region comprising approximately 35% of the 5'UTR was excised. By contrast, a novel splice junction was used in isoforms of MRGPRX1 to include an additional exon upstream of the start codon, consequently adding a region to the 5'UTR. Novel isoforms of HNRNPK were identified, which used previously unannotated splice sites to both excise exon 14 and include a sequence in the 3' end of exon 13. This novel insertion is predicted to introduce a tyrosine phosphorylation site potentially phosphorylated by SRC. We also independently confirm a recently reported DRG-specific splicing event in WNK1 that gives insight into how painless peripheral neuropathy occurs when this gene is mutated. Our findings give a clear overview of mRNA isoform diversity in the human dorsal root ganglia obtained using long-read sequencing.
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Human pain neuroscience and the next generation of pain therapeutics
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Systematic fusion transcript discovery in mantle cell lymphoma using long-read sequencingPreprint
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“While rodents express a relatively simple ASIC3 profile, human ASIC3 displays greater complexity with multiple splice isoforms (e.g. hASIC3a, b, c ) that differ in their C-terminal sequences (Figure 2) [23].”
Yoo, J. J., & Copits, B. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.02.748890
Metadata
- Authors
- Arendt-Tranholm, A., Mwirigi, J. M., & Price, T. J.
- Affiliations
- The University of Texas at Dallas (US)
- Corresponding author
- Price, Theodore J.
- Venue
- Pain
- Published
- 2024-05-16
- Volume
- 165
- Issue
- 11
- Pages
- 2468-2481
- ISSN
- 0304-3959 (ISSN-L)
- 1872-6623
- PMC
- PMC11511651
- OpenAlex
- W4399123201
- Semantic Scholar
- 7e22f1a927ce159a68f15a23481d953500cbbd61
- Cited by
- 10
- References
- 60
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nd
- Locations
- Pain (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (submittedVersion, cc-by-nd)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS065926, U19NS130608)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- RNA isoforms, alternative splicing, dorsal root ganglia, ASIC3, hnRNP K, WNK1, nociception, somatosensory perception, 5' untranslated region, tyrosine phosphorylation, Src kinase, peripheral neuropathy, transcriptome
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