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Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.

Publication ,  Journal Article
Piltonen, M; Parisien, M; Grégoire, S; Chabot-Doré, A-J; Jafarnejad, SM; Bérubé, P; Djambazian, H; Sladek, R; Geneau, G; Willett, P; Stone, LS ...
Published in: Mol Neurobiol
April 2019

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.

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Published In

Mol Neurobiol

DOI

EISSN

1559-1182

Publication Date

April 2019

Volume

56

Issue

4

Start / End Page

2855 / 2869

Location

United States

Related Subject Headings

  • Ribosomes
  • Receptors, Opioid, delta
  • RNA, Messenger
  • Protein Isoforms
  • Protein Biosynthesis
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Male
  • Humans
  • Fetus
 

Citation

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Piltonen, M., Parisien, M., Grégoire, S., Chabot-Doré, A.-J., Jafarnejad, S. M., Bérubé, P., … Diatchenko, L. (2019). Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms. Mol Neurobiol, 56(4), 2855–2869. https://doi.org/10.1007/s12035-018-1253-z
Piltonen, Marjo, Marc Parisien, Stéphanie Grégoire, Anne-Julie Chabot-Doré, Seyed Mehdi Jafarnejad, Pierre Bérubé, Haig Djambazian, et al. “Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.Mol Neurobiol 56, no. 4 (April 2019): 2855–69. https://doi.org/10.1007/s12035-018-1253-z.
Piltonen M, Parisien M, Grégoire S, Chabot-Doré A-J, Jafarnejad SM, Bérubé P, et al. Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms. Mol Neurobiol. 2019 Apr;56(4):2855–69.
Piltonen, Marjo, et al. “Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.Mol Neurobiol, vol. 56, no. 4, Apr. 2019, pp. 2855–69. Pubmed, doi:10.1007/s12035-018-1253-z.
Piltonen M, Parisien M, Grégoire S, Chabot-Doré A-J, Jafarnejad SM, Bérubé P, Djambazian H, Sladek R, Geneau G, Willett P, Stone LS, Shabalina SA, Diatchenko L. Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms. Mol Neurobiol. 2019 Apr;56(4):2855–2869.
Journal cover image

Published In

Mol Neurobiol

DOI

EISSN

1559-1182

Publication Date

April 2019

Volume

56

Issue

4

Start / End Page

2855 / 2869

Location

United States

Related Subject Headings

  • Ribosomes
  • Receptors, Opioid, delta
  • RNA, Messenger
  • Protein Isoforms
  • Protein Biosynthesis
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Male
  • Humans
  • Fetus