TY - JOUR
T1 - Agonist-mediated down-regulation of rat β1-adrenergic receptor transcripts
T2 - Role of potential post-transcriptional degradation factors
AU - Kirigiti, P.
AU - Bai, Y.
AU - Yang, Y. F.
AU - Li, X.
AU - Li, B.
AU - Brewer, G.
AU - Machida, C. A.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035210679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035210679&partnerID=8YFLogxK
U2 - 10.1124/mol.60.6.1308
DO - 10.1124/mol.60.6.1308
M3 - Article
C2 - 11723238
AN - SCOPUS:0035210679
SN - 0026-895X
VL - 60
SP - 1308
EP - 1324
JO - Molecular pharmacology
JF - Molecular pharmacology
IS - 6
ER -