Morphine regulates expression of m-opioid receptor MOR-1A, an intron-retention carboxyl terminal splice variant of the m-opioid receptor (OPRM1) gene via miR-103/miR-107s Journal Article


Authors: Lu, Z.; Xu, J.; Xu, M.; Pasternak, G. W.; Pan, Y. X.
Article Title: Morphine regulates expression of m-opioid receptor MOR-1A, an intron-retention carboxyl terminal splice variant of the m-opioid receptor (OPRM1) gene via miR-103/miR-107s
Abstract: The m-opioid receptor (MOR-1) gene OPRM1 undergoes extensive alternative splicing, generating an array of splice variants. Of these variants, MOR-1A, an intron-retention carboxyl terminal splice variant identical to MOR-1 except for the terminal intracellular tail encoded by exon 3b, is quite abundant and conserved from rodent to humans. Increasing evidence indicates that miroRNAs (miRNAs) regulate MOR-1 expression and that m agonists such as morphine modulate miRNA expression. However, little is known about miRNA regulation of the OPRM1 splice variants. Using 39-rapid amplification cDNA end and Northern blot analyses, we identified the complete 39-untranslated region (39-UTR) for both mouse and human MOR-1A and their conserved polyadenylation site, and defined the role the 39-UTR in mRNA stability using a luciferase reporter assay. Computer models predicted a conserved miR-103/107 targeting site in the 39-UTR of both mouse and human MOR-1A. The functional relevance of miR-103/107 in regulating expression of MOR-1A protein through the consensus miR-103/107 binding sites in the 39-UTR was established by using mutagenesis and a miR-107 inhibitor in transfected human embryonic kidney 293 cells and Be (2)C cells that endogenously express human MOR-1A. Chronic morphine treatment significantly upregulated miR-103 and miR- 107 levels, leading to downregulation of polyribosome- associated MOR-1A in both Be(2)C cells and the striatum of a morphinetolerant mouse, providing a new perspective on understanding the roles of miRNAs and OPRM1 splice variants in modulating the complex actions of morphine in animals and humans. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
Journal Title: Molecular Pharmacology
Volume: 85
Issue: 2
ISSN: 0026-895X
Publisher: The American Society for Pharmacology and Experimental Therapeutics  
Date Published: 2014-02-01
Start Page: 368
End Page: 380
Language: English
DOI: 10.1124/mol.113.089292
PROVIDER: scopus
PMCID: PMC3913361
PUBMED: 24302561
DOI/URL:
Notes: Export Date: 3 February 2014 -- CODEN: MOPMA -- Source: Scopus
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MSK Authors
  1. Yingxian Pan
    108 Pan
  2. Zhigang Lu
    11 Lu
  3. Gavril W Pasternak
    296 Pasternak
  4. Ming Ming Xu
    34 Xu
  5. Jin   Xu
    50 Xu