Format

Send to

Choose Destination
See comment in PubMed Commons below
Biol Psychiatry. 2009 Apr 15;65(8):702-5. doi: 10.1016/j.biopsych.2008.11.024. Epub 2009 Jan 9.

Differential allelic expression of dopamine D1 receptor gene (DRD1) is modulated by microRNA miR-504.

Author information

1
Departments of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia 22911, USA.

Abstract

BACKGROUND:

Previously, we reported that dopamine D1 receptor gene (DRD1) is associated with nicotine dependence (ND) and demonstrated that two alleles (A and G) of polymorphism rs686 in the 3'-untranslated region (3'UTR) of DRD1 are expressed differentially. However, the mechanism underlying the differential expression remains to be determined. We hypothesize that it is caused by miRNA targeting.

METHODS:

We first used the MicroInspector algorithm to identify microRNAs (miRNAs) potentially targeting the rs686 polymorphism in the DRD1 3'UTR and then employed a luciferase reporter assay combined with site-directed mutagenesis to test the predicted miRNA targeting. We also examined the miRNA targeting of DRD1 with a gene expression assay.

RESULTS:

Of two miRNAs predicted by computational analyses, we found that miR-504, not miR-296, upregulated reporter luciferase activity and increased DRD1 expression by targeting the DRD1 3' UTR, whereas inhibition of miR-504, not miR-296, had the opposite effect. Furthermore, we showed that the direct binding of miR-504 to the DRD1 3'UTR, verified by site-directed mutagenesis, causes a significant expression difference between the two alleles.

CONCLUSIONS:

miR-504 up-regulates DRD1 expression by direct binding to the 3'UTR, which leads to differential allele-specific expression of DRD1.

PMID:
19135651
PMCID:
PMC2678413
DOI:
10.1016/j.biopsych.2008.11.024
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center