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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