D1 dopamine receptor post‐transcriptional regulation in the CAD catecholaminergic cell line

Abstract

The D1 dopamine receptor has been implicated in various addictive behaviors. We have demonstrated that this receptor is post‐transcriptionally regulated (PTR) both in vivo and in vitro. The objective of our study is to determine the molecular mechanisms that mediate D1 receptor PTR. The CAD catecholaminergic cell line expresses endogenous D1 receptor. Upon serum deprivation‐induced differentiation, there is an increase in D1 receptor mRNA expression but not protein. Here we show that the 3′ untranslated region (UTR) is necessary and sufficient for D1 receptor PTR. Deletion and competition studies suggest that the PTR is mediated by a trans‐acting factor interacting within the first 1277 bp of the D1 3'UTR. Dicer knockdown studies indicated a role for micro‐RNAs (miRs). To identity the miRs involved in D1 receptor PTR we compared the global expression profile of all known miRs in non‐differentiated and differentiated CAD cells. Funded by The FM Kirby Foundation and NIH (R03 DA026030) grants to EVK and a PhRMA Foundation Pre‐Doctoral Fellowship to KT.