Dataset Information

Post-transcriptional regulation of mouse mu opioid receptor (MOR1) via its 3' untranslated region: a role for microRNA23b.

ABSTRACT: 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.

SUBMITTER: Wu Q

PROVIDER: S-EPMC2614608 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Post-transcriptional regulation of mouse mu opioid receptor (MOR1) via its 3' untranslated region: a role for microRNA23b.

Wu Qifang Q Law Ping-Yee PY Wei Li-Na LN Loh Horace H HH

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20080820 12

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 micr ...[more]

PMID: 18716031

Similar Datasets

Project description:To investigate the importance of the 3'-untranslated region (UTR) of the mouse cholesterol 7alpha-hydroxylase (cyp7) mRNA in post-transcriptional regulation of expression of the cyp7 gene, chimaeric genes encoding mRNA containing the structural sequence of chloramphenicol acetyltransferase (CAT) linked to either the 3'-UTR of the mouse cyp7 mRNA or the SV40 early gene mRNA were constructed. The human cytomegalovirus (CMV) promoter was used to drive the expression of all the chimaeric genes. Thus the transgenes had identical sequences in the promoter, the regions encoding the 5'-UTR and translated sequence but differed in the region encoding the 3'-UTR of their respective mRNA species. The transgene containing the entire cyp7 3'-UTR (designated CMV.CAT.CYP7) gave rise to CAT activity in transfected hepatoma cells that was one-quarter of that obtained in cells transfected with the transgene containing the SV40 3'-UTR (designated CMV.CAT.SV40). The 3'-UTR of the cyp7 mRNA contains sequences resembling AU-rich elements (AREs). Deleting eight of nine putative AREs from the CYP7 3'-UTR sequence increased the CAT activity to a level greater than that observed for CMV.CAT. SV40, whereas deletion of the intron region had no effect. These results show that the AREs of the 3'-UTR of the cyp7 mRNA decrease transgene expression. Bile acids are known to repress the expression of the cyp7 gene. To test whether the 3'-UTR of the cyp7 mRNA has a role in this process, the expression of the chimaeric genes was evaluated in hepatoma cells competent for bile acid uptake. Conjugated bile acids, but not unconjugated bile acids, further decreased the expression of the CMV.CAT.CYP7 transgene. The same bile acids had no effect on the expression of the CMV.CAT.SV40 transgene. Deletion of the intron from the cyp7 sequence did not alter the CAT activity compared with the parental plasmid, and also did not alter the sensitivity of the transgene to the conjugated bile acids. Deletion of the AREs from the cyp7 3'-UTR, which increased the expression of the transgene, did not abolish the sensitivity of the transgene to repression by conjugated bile acids. Thus the 3'-UTR of the mouse cyp7 mRNA also contains elements that facilitate the further repression of transgene expression in the presence of conjugated bile acids. The results indicate that the 3'-UTR of the mouse cyp7 mRNA contains information specifying regulation at the post-transcriptional level.

Dataset Information

Post-transcriptional regulation of mouse mu opioid receptor (MOR1) via its 3' untranslated region: a role for microRNA23b.

Publications

Post-transcriptional regulation of mouse mu opioid receptor (MOR1) via its 3' untranslated region: a role for microRNA23b.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets