Agonist-mediated destabilization of human beta1-adrenergic receptor mRNA: role of the 3' untranslated translated region

Biochem Biophys Res Commun. 1998 Nov 18;252(2):357-62. doi: 10.1006/bbrc.1998.9598.

Abstract

For proto-oncogenes and cytokines, regulation of gene expression at the level of mRNA stability is well established. In contrast, there is comparatively limited knowledge regarding this mechanism of regulation for G-protein-coupled receptors. To explore this process further, the human beta1-adrenergic receptor (AR) was stably expressed in tsAF8 cells. Treatment with beta-agonist decreased the half-life of beta1-AR mRNA by approximately 50%. Removal of the 3'UTR from the beta1-AR (coding region only) dramatically stabilized mRNA. Additionally, in a chimeric mRNA, the beta1-AR 3'UTR was able to target the normally highly stable beta-globin mRNA for accelerated decay. However, the chimera did not undergo agonist-mediated destabilization indicating that the 3'UTR may be "necessary but not sufficient" for agonist-mediated mRNA destabilization. Inhibition of translation significantly stabilized beta1-AR mRNA (approximately 2-fold); however, pretreatment of cells with beta-agonist prior to translational arrest produced the same degree of mRNA destabilization indicating that agonist-mediated destabilization may be independent of the translation process. Conversely, translational inhibition simultaneous with beta-agonist exposure abrogated agonist-mediated destabilization indicating a dependence on de novo protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Adrenergic beta-Agonists / pharmacology
  • Cell Line
  • Cycloheximide / pharmacology
  • Drug Stability
  • Half-Life
  • Humans
  • Isoproterenol / pharmacology
  • Protein Biosynthesis / drug effects
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • Receptors, Adrenergic, beta-1 / genetics*
  • Transfection

Substances

  • 3' Untranslated Regions
  • Adrenergic beta-Agonists
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Cycloheximide
  • Isoproterenol