Characterization of two human beta1-adrenergic receptor transcripts: cloning and alterations in the failing heart.

Two human beta1-adrenergic receptor cDNAs, approximately 2.75 kb and approximately 3 kb in length, were isolated from a placenta phage library. Both transcripts are collinear with the previously isolated genomic sequence. Additionally, all clones begin between -274 and -236 bp relative to the translational start site, which is consistent with the previously identified transcriptional start site at -263. Furthermore, the 2.75 and 3 kb transcripts utilize conserved polyadenylation consensus sites at +2469 and +2751, respectively. Thus, this is the first report of the identification of full-length human beta1-AR cDNA clones. Both transcripts are expressed in placenta, heart, cerebral cortex, and lung with the 3 kb transcript more highly expressed than the 2.75 kb transcript in all tissues. RNase protection analysis utilizing left ventricular heart RNA isolated from patients with idiopathic dilated cardiomyopathy demonstrates 2.1-fold and 2.7-fold decreases of the 2. 75 and 3 kb transcripts, respectively, as compared with nonfailing controls. Thus, in heart failure patients the 3 kb transcript decreases to a significantly greater extent than the 2.75 kb transcript. This preferential reduction may be the result of differences in mRNA stability mediated by putative AU-rich elements specific to the 3'-untranslated region of the larger transcript.