Morphine modulates the expression of mu-opioid receptor exon 5-associated full-length C-terminal splice variants by upregulating miR-378a-3p Journal Article


Authors: Lu, Z.; Xu, J.; Wang, Q.; Pan, Y. X.
Article Title: Morphine modulates the expression of mu-opioid receptor exon 5-associated full-length C-terminal splice variants by upregulating miR-378a-3p
Abstract: The mu-opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating an array of splice variants that are conserved from rodent to human. Both mouse and human OPRM1 have five exon 5-associated seven transmembrane full-length carboxyl terminal variants, MOR-1B1, MOR-1B2, MOR-1B3, MOR-1B4, and MOR-1B5, all of which are derived from alternative 3′ splicing from exon 3 to alternative sites within exon 5. The functional relevance of these exon 5-associated MOR-1Bs has been demonstrated in mu agonist-induced G protein coupling, adenylyl cyclase activity, receptor internalization and desensitization, and post-endocytic sorting, as well as region-specific expression at the mRNA level. In the present study, we mapped a polyadenylation site for both mouse and human MOR-1Bs that defines the 3′-untranslated regions (3′-UTR) of MOR-1Bs and stabilizes mMOR-1Bs mRNAs. We identified a conserved miR378a-3p sequence in the 3′-UTR of both mouse and human MOR-1BS transcripts through which miR-378a-3p can regulate the expression of MOR-1Bs at the mRNA level. Chronic morphine treatment significantly increased the miR-378-3p level in Be(2)C cells and the brainstem of the morphine tolerant mice, contributing to the decreased expression of the mouse and human MOR-1B3 and MOR-1B4. Our study provides new insights into the role of miRNAs and Oprm1 splice variants in morphine tolerance. © 2020 Federation of American Societies for Experimental Biology
Keywords: controlled study; protein expression; unclassified drug; gene sequence; human cell; exon; nonhuman; animal cell; mouse; animal tissue; microrna; carboxy terminal sequence; animal experiment; gene expression regulation; down regulation; upregulation; 3' untranslated region; morphine; opioid; brain stem; mu opiate receptor; morphine tolerance; splicing; polyadenylation; oprm1; human; male; priority journal; article; mrna expression level; microrna 378a 3p; sk-n-be(2)-c cell line
Journal Title: FASEB Journal
Volume: 34
Issue: 3
ISSN: 0892-6638
Publisher: Federation of American Societies for Experimental Biology  
Date Published: 2020-03-01
Start Page: 4540
End Page: 4556
Language: English
DOI: 10.1096/fj.201901879RR
PUBMED: 31999011
PROVIDER: scopus
PMCID: PMC7060099
DOI/URL:
Notes: Article -- Export Date: 1 April 2020 -- Source: Scopus
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  1. Yingxian Pan
    132 Pan
  2. Jin   Xu
    60 Xu