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

Abstract

Transcription-start sites for the mouse and human beta 3-adrenergic-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 beta 3-adrenergic-receptor expression by glucocorticoids and by beta-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 beta 3-adrenergic-receptor genes to those of the corresponding cDNA revealed that in contrast to beta 1 and beta 2 adrenergic receptors, the beta 3-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 beta 3 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 beta 3-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 beta 3-adrenergic-receptor transcripts which are differentially expressed in white and brown adipose tissues. Human beta 3-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 beta 3-adrenergic-receptors expression.

Thiazolidinediones inhibit the expression of beta3-adrenergic receptors at a transcriptional level.

“…Another possibility is the existence of a comparatively small pool of ␤ 3 -AR mRNA, ~20% of the total, that is more stable. An alternate ␤ 3 -AR mRNA splice variant has been identified in mouse BAT and WAT (24) and also in 3T3-F442A cells (34). Our assay does not distinguish these variants, and even though Granneman and Lahners (34) did not find that they are differentially regulated by cAMP, the possibility that one of them has a longer life span in HIB-1B cells remains to be tested.…”

Decreased Expression of Adrenomedullin during Adipocyte-Differentiation of 3T3-L1 Cells

“…It was reported that all three isoforms of RAMPs, RAMP-1, -2, and -3, are expressed in adipose tissue (26). The β3-adrenergic receptor, predominantly expressed in adipocytes, mediates the catecholamine action on lipolysis, and there are cAMP-response elements in the promoter of the β3-adrenergic receptor gene (27,28). It is therefore tempting to speculate that AM may modulate the expression of β3-adrenergic receptors via the cAMP pathway as an autocrine and/or paracrine factor, and this matter will require further investigation.…”

Mouse β3a‐ and β3b‐adrenoceptors expressed in Chinese hamster ovary cells display identical pharmacology but utilize distinct signalling pathways

“…The mouse b 3 -adrenoceptor (AR) gene contains two introns, both of which undergo alternate splicing (van Spronsen et al, 1993;Granneman & Lahners, 1995;Evans et al, 1999). Splicing of intron A at a novel acceptor site 100 bp upstream from the previously characterized start of exon 2 results in the production of mRNA encoding a b 3 -AR variant, termed the b 3b -AR.…”

“…This receptor has a unique Cterminal tail, with 17 amino acids (SSLLREPRHLYTCLb 3b -AR transcripts in brown adipose tissue (BAT), and the highest in hypothalamus (Evans et al, 1999). Previous studies in mice have shown that alternate splice acceptor sites result in the generation of two b 3 -AR transcripts that di er in the 3' untranslated regions (van Spronsen et al, 1993: Granneman & Lahners, 1995. These transcripts have di ering tissue expression in WAT and BAT, with the shorter transcript predominant in WAT, and the longer transcript in BAT.…”