Characterization of Two Human β1-Adrenergic Receptor Transcripts: Cloning and Alterations in the Failing Heart

The human beta1-adrenergic receptor (AR) and hamster beta2-AR transcripts can be post-transcriptionally regulated at the level of mRNA stability and undergo accelerated agonist-mediated degradation via interaction of their 3' untranslated regions (UTR) with RNA binding proteins. Using RNase protection assays, we have determined that chronic isoproterenol exposure of rat C6 glioma cells results in the accelerated reduction of beta1-AR mRNAs. To determine the role of cellular environment on the agonist-independent and agonist-mediated degradation of beta1-AR mRNAs, we transfected rat beta1-AR expression recombinants into both hamster DDT1MF2 cells and rat L6 cells. The rat beta1-AR mRNAs in the two transfectant cell pools retain longer agonist-independent half-lives than in the C6 environment and undergo accelerated degradation upon chronic agonist exposure. Using UV-cross-linking/immunoblot and immunoprecipitation analyses, we have determined that the rat beta1-AR 3' UTR recognizes a predominant M(r) 39,000 component, identified as the mammalian elav-like protein HuR, and several other minor components, including the heteronuclear protein hnRNP A1. HuR levels are more highly expressed in C6 cells than in DDT1MF2 and L6 cells and are induced after chronic isoproterenol treatment. Furthermore, C6 transfectants containing an HuR expression recombinant exhibit reduced beta1-AR mRNA half-lives that were statistically comparable with half-lives identified in isoproterenol-treated C6 cells. These results imply that HuR plays a potential role in the agonist-independent and agonist-mediated down-regulation of beta1-AR mRNAs.

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Characterization of Two Human β1-Adrenergic Receptor Transcripts: Cloning and Alterations in the Failing Heart

Cited by 2 publications

References 25 publications

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Agonist-Mediated Down-Regulation of Rat β₁-Adrenergic Receptor Transcripts: Role of Potential Post-Transcriptional Degradation Factors

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Characterization of Two Human β1-Adrenergic Receptor Transcripts: Cloning and Alterations in the Failing Heart

Cited by 2 publications

References 25 publications

Comparative physiology, pharmacology and toxicology of β-blockers: Mammals versus fish

Comparative physiology, pharmacology and toxicology of β-blockers: Mammals versus fish

Agonist-Mediated Down-Regulation of Rat β1-Adrenergic Receptor Transcripts: Role of Potential Post-Transcriptional Degradation Factors

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Product

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Agonist-Mediated Down-Regulation of Rat β₁-Adrenergic Receptor Transcripts: Role of Potential Post-Transcriptional Degradation Factors