Agonist-mediated destabilization of human β1-adrenergic receptor mRNA:: Role of the 3′ untranslated translated region

For proto-oncogenes and cytokines, regulation of gene expression at the level of mRNA stability is well established. In contrast, there is comparatively limited knowledge regarding this mechanism of regulation for G-protein-coupled receptors. To explore this process further, the human beta(1)-adrenergic receptor (AR) was stably expressed in tsAF8 cells. Treatment with beta-agonist decreased the half-life of beta(1)-AR mRNA by similar to 50%. Removal of the 3'UTR from the beta(1)-AR (coding region only) dramatically stabilized mRNA. Additionally, in a chimeric mRNA, the beta(1)-AR 3'UTR was able to target the normally highly stable beta-globin mRNA for accelerated decay. However, the chimera did not undergo agonist-mediated destabilization indicating that the 3'UTR may be "necessary but not sufficient" for agonist-mediated mRNA destabilization. Inhibition of translation significantly stabilized beta(1)-AR mRNA (similar to 2-fold); however, pretreatment of cells with beta-agonist prior to translational arrest produced the same degree of mRNA destabilization indicating that agonist-mediated destabilization may be independent of the translation process. Conversely, translational inhibition simultaneous with beta-agonist exposure abrogated agonist-mediated destabilization indicating a dependence on de novo protein synthesis. (C) 1998 Academic Press.