Post-transcriptional regulation of mouse mu opioid receptor (MOR1) via its 3' untranslated region: a role for microRNA23b.
Expression of the mu opioid receptor (MOR1) protein is regulated temporally and spatially. Although transcription of its gene has been studied extensively, regulation of MOR1 protein production at the level of translation is poorly understood. Using reporter assays, we found that the MOR1 3'-untranslated region (UTR) represses reporter expression at the post-transcriptional level. Suppression by the 3'-UTR of MOR1 is mediated through decreased mRNA association with polysomes, which requires microRNA23b (miRNA23b), a specific miRNA that is expressed in mouse brain and NS20Y mouse neuroblastoma cells. miRNA23b interacts with the MOR1 3'-UTR via a K box motif. By knocking down endogenous miRNA23b in NS20Y cells, we confirmed that miRNA23b inhibits MOR1 protein expression in vivo. This is the first study reporting a translationally repressive role for the MOR1 3'-UTR. We propose a mechanism in which miRNA23b blocks the association of MOR1 mRNA with polysomes, thereby arresting its translation and suppressing the production of MOR1 protein.
Wu
Qifang
Q
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. wuxx0285@umn.edu
Law
Ping-Yee
PY
Wei
Li-Na
LN
Loh
Horace H
HH
D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D011132:Polyribosomes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection
D020413:3' Untranslated Regions; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu