Deletion and site-directed mutagenesis studies showed that the D1 receptor post-transcriptional regulation in CAD cells is mediated by a specific interaction of miRNA miR142-3p with a single cis-element adjacent to the first poly adenylation signal site in the D1 receptor 39UTR. Posttranscriptional regulation of 
many genes is mediated by miRNA. These,22 nucleotide long endogenous RNA molecules are partially complementary to nucleotide sequences in the 39UTR of genes. By binding to the 39UTR with partial complementarity, miRNA molecules have been reported to repress translation of the mRNA or affect mRNA stability. Previous studies have shown that miRNAs modulate expression of various G-protein coupled receptors including the Folinic acid calcium salt pentahydrate b-adrenergic receptor, adenosine A2A receptor, serotonin receptors and estrogen receptor a. Our results add D1 dopamine receptors to the growing list of G-protein coupled receptors whose expression is regulated by miRNAs. D1 receptors couple to activate adenylate cyclase, increasing intracellular cAMP levels. The increased cAMP activates the cAMP-dependent kinase which in turn phosphorylates the protein phosphatase DARPP-32. Activation of D1 receptors is known to increase phosphorylated DARPP-32 levels both in vitro and in vivo. The regulation of endogenous D1 receptor expression by miR142-3p is biologically significant as inhibition of miR-142-3p increased endogenous D1 receptor protein levels and Mechlorethamine hydrochloride enhanced D1 receptor signaling as evidenced by increased cAMP production and phospo-DARPP-32 levels. Finally, we showed that the expression of miR-142-3p was inversely correlated to D1 receptor protein expression during postnatal mouse brain development. To our knowledge this is the first report of a microRNA mediated translational suppression of any of the five dopamine receptor subtypes. One previous study showed that miR-504 specifically targets a polymorphic site in human D1 39UTR that is associated with nicotine dependence; however in that study miR-504 was found to increase, rather than decrease, the expression level of the human D1 receptor mRNA. The identification of miR-142-3p as a regulator of D1 receptor expression was unexpected as the function of this microRNA has been previously described only in hematopoietic cells and lymphocytes were it was shown to modulate the differentiation of various classes of T-cells. The expression of miR-142-3p is particularly high in the antigen-presenting dendritic cells. Interestingly, lipopolysaccharide treatment decreases the expression of miR-142-3p in dendritic cells, specifically relieving the translational repression of the interleukin-6 mRNA and increasing the level of secreted IL-6. Circulating levels of IL-6 is high in schizophrenic patients and administration of IL-6 has been reported to increase stereotypic behavior in rodent models. IL-6 along with TGF-b has also been shown to promote the differentiation of naive T-cells into the T-helper, Th-17 cells. Interestingly, antagonizing D1 receptor function inhibits the differentiation of Th-17 cells. Recent studies have shown that functional D1 dopamine receptors are expressed in dendritic cells and naive T-cells and the specific activation of these D1 receptors by dopamine promotes the differentiation of the Tcells into Th-2 and Th-17 cells. An earlier study showed that D1 dopamine receptors suppress the differentiation of naive T-cells into regulatory T-cells cells that are involved in the immune suppression response. Our observations suggest that miR-142-3p mediated regulation of D1 receptor expression might contribute to T-cell differentiation.