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Nucleic Acids Research Advance Access published online on February 6, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm034
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Translational repression of mouse mu opioid receptor expression via leaky scanning

Kyu Young Song*, Cheol Kyu Hwang, Chun Sung Kim, Hack Sun Choi, Ping-Yee Law, Li-Na Wei and Horace H. Loh

Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

*To whom Correspondence should be addressed. Tel: +1 612 626 6539; Fax: +1 612 625 8408; Email: songx047{at}umn.edu

Received November 15, 2006. Revised December 10, 2006. Accepted January 7, 2007.

Mu opioid receptor (MOR) expression is under temporal and spatial controls, but expression levels of the MOR gene are relatively low in vivo. In addition to transcriptional regulations, upstream AUGs (uAUGs) and open reading frames (uORFs) profoundly affect the translation of the primary ORF and thus the protein levels in several genes. The 5'-untranslated region (UTR) of mouse MOR mRNA contains three uORFs preceding the MOR main initiation codon. In MOR-fused EGFP or MOR promoter/luciferase reporter constructs, mutating each uAUG individually or in combinations increased MOR transient heterologous expression in neuroblastoma NMB and HEK293 cells significantly. Translation of such constructs increased up to 3-fold without altering the mRNA levels if either the third uAUG or both the second and third AUGs were mutated. Additionally, these uAUG-mediated translational inhibitions were independent of their peptide as confirmed by internal mutation analyses in each uORF. Translational studies indicated that protein syntheses were initiated at these uAUG initiation sites, with the third uAUG initiating the highest translation level. These results support the hypothesis that uORFs in mouse MOR mRNA act as negative regulators through a ribosome leaky scanning mechanism. Such leaky scanning resulted in the suppression of mouse MOR under normal conditions.


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 Mol. Cell. ProteomicsHome page
H. S. Choi, K. Y. Song, C. K. Hwang, C. S. Kim, P.-Y. Law, L.-N. Wei, and H. H. Loh
A Proteomics Approach for Identification of Single Strand DNA-binding Proteins Involved in Transcriptional Regulation of Mouse {micro} Opioid Receptor Gene
Mol. Cell. Proteomics, August 1, 2008; 7(8): 1517 - 1529.
[Abstract] [Full Text] [PDF]


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