The Mr 35,000 β-adrenergic receptor mRNA-binding protein binds transcripts of G-protein-linked receptors which undergo agonist-induced destabilization

Abstract

The Mr 35,000 β-adrenergic receptor mRNA-binding protein, termed β-ARB protein, is induced by β-adrenergic agonists and binds to β2-receptor mRNAs that display agonist-induced destabilization. Recently a cognate sequence in the mRNA was identified that provides for recognition by β-ARB protein. In the present work we test the ability of the β-ARB to discriminate among G-protein-linked receptor mRNAs that either do or do not display agonist-induced destabilization and test the predictive value of the presence of the cognate sequence to identify receptors displaying post-transcriptional regulation. Transcripts of β2-, but not rat β1-, rat β3-, or human β3-adrenergic receptors bind β-ARB protein, linking agonist-induced destabilization of mRNA to transcripts with the cognate sequence. Scanning GeneBank for G-protein-linked receptor transcripts with the cognate sequence revealed several candidates, including the thrombin receptor. We demonstrate that the thrombin receptor mRNA is recognized by β-ARB protein and like the β2-receptor is regulated post-transcriptionally by agonist and cAMP. Thus, the domain of regulation by β-ARB protein includes transcripts of G-protein-linked receptors other than β2-adrenergic receptors.