Agonist-mediated down-regulation of rat β1-adrenergic receptor transcripts: Role of potential post-transcriptional degradation factors

P. Kirigiti, Y. Bai, Y. F. Yang, X. Li, B. Li, G. Brewer, C. A. Machida

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The human β1-adrenergic receptor (AR) and hamster β2-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 β1-AR mRNAs. To determine the role of cellular environment on the agonist-independent and agonist-mediated degradation of β1-AR mRNAs, we transfected rat β1-AR expression recombinants into both hamster DDT1MF2 cells and rat L6 cells. The rat β1-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 β1-AR 3′ UTR recognizes a predominant Mr 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 β1-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 β1-AR mRNAs.

Original languageEnglish (US)
Pages (from-to)1308-1324
Number of pages17
JournalMolecular pharmacology
Volume60
Issue number6
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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