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Both mouse and human\n                    <jats:italic>OPRM1<\/jats:italic>\n                    have five exon 5\u2010associated seven transmembrane full\u2010length carboxyl terminal variants, MOR\u20101B1, MOR\u20101B2, MOR\u20101B3, MOR\u20101B4, and MOR\u20101B5, all of which are derived from alternative 3\u2032 splicing from exon 3 to alternative sites within exon 5. The functional relevance of these exon 5\u2010associated MOR\u20101Bs has been demonstrated in mu agonist\u2010induced G protein coupling, adenylyl cyclase activity, receptor internalization and desensitization, and post\u2010endocytic sorting, as well as region\u2010specific expression at the mRNA level. In the present study, we mapped a polyadenylation site for both mouse and human MOR\u20101Bs that defines the 3\u2032\u2010untranslated regions (3\u2032\u2010UTR) of MOR\u20101Bs and stabilizes mMOR\u20101Bs mRNAs. We identified a conserved miR378a\u20103p sequence in the 3\u2032\u2010UTR of both mouse and human MOR\u20101B\n                    <jats:sub>S<\/jats:sub>\n                    transcripts through which miR\u2010378a\u20103p can regulate the expression of MOR\u20101Bs at the mRNA level. Chronic morphine treatment significantly increased the miR\u2010378\u20103p 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\u20101B3 and MOR\u20101B4. Our study provides new insights into the role of miRNAs and\n                    <jats:italic>Oprm1<\/jats:italic>\n                    splice variants in morphine tolerance.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901879rr","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T05:46:26Z","timestamp":1580363186000},"page":"4540-4556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Morphine modulates the expression of mu\u2010opioid receptor exon 5\u2010associated full\u2010length C\u2010terminal splice variants by upregulating miR\u2010378a\u20103p"],"prefix":"10.1096","volume":"34","author":[{"given":"Zhigang","family":"Lu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Pharmacy Nanjing University of Chinese Medicine Nanjing China"},{"name":"The Affiliated Hospital of Nanjing 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