The promoter and intron/exon structure of the human and mouse β3‐adrenergic‐receptor genes

Transcription‐start sites for the mouse and human β3‐adrergic‐receptor mRNA have been localized in a region comprised between 150 and 200 nucleotides 5′ from the ATG translation‐start codon. Motifs potentially implicated in heterologous regulation of β3‐adrenergic‐receptor expression by glucocorticoids and by β‐adrenergic agonists have been identified upstream from these cap sites. In mouse, a second mRNA initiation region is postulated to exist further upstream. Comparison of the nucleotide sequences of the 3′ end of the human and mouse β3‐adrenergic‐receptor genes to those of the corresponding cDNA revealed that in contrast to β1 and β2 adrenergic receptors, the β3‐adrenergic‐receptor genes comprise several exons. A large exon (1.4 kb) encodes the first 402 and 388 amino‐acid residues of the human and mouse β3‐adrenergic‐receptor, respectively. In man, a second exon (700 bp) contains the sequence coding for the six carboxy‐terminal residues of the receptor and the entire mRNA 3′ untranslated region. In mouse, a second exon (68 bp) codes for the 12 carboxy‐terminal residues of the receptor and a third exon contains the β3‐adrenergic‐receptor mRNA 3′ untranslated region. The use of alternate acceptor splice sites generates two forms of exon 3 (600 bp and 700 bp), yielding two β3‐adrenergic‐receptor transcripts which are differentially expressed in white and brown adipose tissues. Human β3‐adrenergic‐receptor transcripts with different 3′ untranslated regions are produced by continuation of transcription beyond termination signals. Together, our results suggest that utilization of alternate promoters and/or 3′ untranslated regions may allow tissue‐specific regulation of β3‐adrenergic‐receptors expression.