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• W2030658643 abstract "The <i>μ</i>-opioid receptor (MOR-1) gene <i>OPRM1</i> 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 <i>μ</i> agonists such as morphine modulate miRNA expression. However, little is known about miRNA regulation of the <i>OPRM1</i> splice variants. Using 3′-rapid amplification cDNA end and Northern blot analyses, we identified the complete 3′-untranslated region (3′-UTR) for both mouse and human MOR-1A and their conserved polyadenylation site, and defined the role the 3′-UTR in mRNA stability using a luciferase reporter assay. Computer models predicted a conserved miR-103/107 targeting site in the 3′-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 3′-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 morphine-tolerant mouse, providing a new perspective on understanding the roles of miRNAs and <i>OPRM1</i> splice variants in modulating the complex actions of morphine in animals and humans." @default.
• W2030658643 created "2016-06-24" @default.
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• W2030658643 date "2013-12-03" @default.
• W2030658643 modified "2023-10-18" @default.
• W2030658643 title "Morphine Regulates Expression of<i>μ</i>-Opioid Receptor MOR-1A, an Intron-Retention Carboxyl Terminal Splice Variant of the<i>μ</i>-Opioid Receptor (<i>OPRM1</i>) Gene via miR-103/miR-107" @default.
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• W2030658643 doi "https://doi.org/10.1124/mol.113.089292" @default.
• W2030658643 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3913361" @default.
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