Title |
Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms
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Published in |
Molecular Neurobiology, July 2018
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DOI | 10.1007/s12035-018-1253-z |
Pubmed ID | |
Authors |
Marjo Piltonen, Marc Parisien, Stéphanie Grégoire, Anne-Julie Chabot-Doré, Seyed Mehdi Jafarnejad, Pierre Bérubé, Haig Djambazian, Rob Sladek, Geneviève Geneau, Patrick Willett, Laura S. Stone, Svetlana A. Shabalina, Luda Diatchenko |
Abstract |
The delta-opioid receptor (DOPr) participates in mediating the effects of opioid analgesics. However, no selective agonists have entered clinical care despite potential to ameliorate many neurological and psychiatric disorders. In an effort to address the drug development challenges, the functional contribution of receptor isoforms created by alternative splicing of the three-exonic coding gene, OPRD1, has been overlooked. We report that the gene is transcriptionally more diverse than previously demonstrated, producing novel protein isoforms in humans and mice. We provide support for the functional relevance of splice variants through context-dependent expression profiling (tissues, disease model) and conservation of the transcriptional landscape in closely related vertebrates. The conserved alternative transcriptional events have two distinct patterns. First, cassette exon inclusions between exons 1 and 2 interrupt the reading frame, producing truncated receptor fragments comprising only the first transmembrane (TM) domain, despite the lack of exact exon orthologues between distant species. Second, a novel promoter and transcriptional start site upstream of exon 2 produces a transcript of an N-terminally truncated 6TM isoform. However, a fundamental difference in the exonic landscaping as well as translation and translation products poses limits for modelling the human DOPr receptor system in mice. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Scientists | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 24 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 17% |
Other | 2 | 8% |
Researcher | 2 | 8% |
Professor | 1 | 4% |
Student > Master | 1 | 4% |
Other | 1 | 4% |
Unknown | 13 | 54% |
Readers by discipline | Count | As % |
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Neuroscience | 2 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Agricultural and Biological Sciences | 1 | 4% |
Biochemistry, Genetics and Molecular Biology | 1 | 4% |
Medicine and Dentistry | 1 | 4% |
Other | 1 | 4% |
Unknown | 17 | 71% |