Long-term morphine treatment decreases the association of mu-opioid receptor (MOR1) mRNA with polysomes through miRNA23b.
Mu-opioid receptor (MOR) mediates most of the pharmacological effects of opioid drugs. The expression of MOR is temporarily and spatially regulated at both the transcriptional and post-transcriptional levels. Long-term morphine treatment that induces tolerance does not alter MOR mRNA expression, suggesting no direct link between agonist treatment and MOR gene transcription. We previously identified the 3'-untranslated region (3'-UTR) of the major transcript of mu-opioid receptor (MOR1) and revealed a novel trans-acting factor, miRNA23b, that binds to the K box motif in the 3'-UTR. The interaction between miRNA23b with the MOR1 3'-UTR suppressed receptor translation by inhibiting polysome-mRNA association. In this report, we demonstrate that long-term morphine treatment increases miRNA23b expression in a dose- and time-dependent manner and represses the association of MOR1 mRNA with polysomes through the MOR1 3'-UTR. The translational luciferase reporter assay shows a suppression effect of morphine on reporter activity that requires the MOR1 3'-UTR. This suggests a potential link between MOR expression and morphine treatment at the post-transcriptional level in which a specific miRNA, miRNA23b, is involved.
Wu
Qifang
Q
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St. S.E., Minneapolis, MN 55455, USA. wuxx0285@umn.edu
Zhang
Lei
L
Law
Ping-Yee
PY
Wei
Li-Na
LN
Loh
Horace H
HH
D000818:Animals; D002460:Cell Line; D006801:Humans; D049410:Luciferases, Renilla / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009020:Morphine / Q000008:administration & dosage*; D011132:Polyribosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D009020:Morphine; D049410:Luciferases, Renilla