%0 Journal Article %1 Danner1998 %A Danner, S. %A Frank, M. %A Lohse, M. J. %D 1998 %J J Biol Chem %K Adrenergic Animals Binding Cell Complementary Cricetinae DNA, Down-Regulation Fusion Globins/genetics Humans Line Messenger/*genetics Protein Proteins/genetics/metabolism RNA, RNA-Binding Recombinant beta-2/*agonists/genetics/metabolism beta-Agonists/*pharmacology Receptor %N 6 %P 3223-9 %T Agonist regulation of human beta2-adrenergic receptor mRNA stability occurs via a specific AU-rich element %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9452435 %V 273 %X Prolonged agonist stimulation of beta2-adrenergic receptors results in receptor down-regulation, which is closely associated with a reduction of the corresponding mRNA, an effect mediated in part by changes in mRNA stability. Transfection experiments with human beta2-adrenergic receptor cDNAs bearing or lacking the untranslated regions suggested that the essential agonist sensitivity of the mRNA resides within the 3'-untranslated region. The importance of this region was further confirmed in gel shift experiments; cytosolic preparations from agonist-stimulated DDT1-MF2 smooth muscle cells caused a shift of beta2-adrenergic receptor mRNAs containing the 3'-untranslated region. Progressive 3'-terminal truncations of the receptor cDNA led to the identification of an AU-rich element at positions 329-337 of the 3'-untranslated region as the responsible cis-acting element. Substitution of this motif by cytosine residues almost completely abolished mRNA down-regulation and inhibited the formation of the RNA-protein complex. Even though the beta2-adrenergic receptor AU-rich element showed two U --> A transitions compared with the recently proposed AU-rich element consensus sequence, it revealed an almost identical destabilizing potency. Fusion of the beta2-adrenergic receptor 3'-untranslated region to the beta-globin coding sequence dramatically reduced the half-life of the chimeric transcript in an agonist- and cAMP-dependent manner. This suggests that the agonist-induced beta2-adrenergic receptor mRNA destabilization is regulated by cAMP-dependent RNA-binding protein(s) via a specific AU-rich element.

@article{Danner1998, abstract = {Prolonged agonist stimulation of beta2-adrenergic receptors results in receptor down-regulation, which is closely associated with a reduction of the corresponding mRNA, an effect mediated in part by changes in mRNA stability. Transfection experiments with human beta2-adrenergic receptor cDNAs bearing or lacking the untranslated regions suggested that the essential agonist sensitivity of the mRNA resides within the 3'-untranslated region. The importance of this region was further confirmed in gel shift experiments; cytosolic preparations from agonist-stimulated DDT1-MF2 smooth muscle cells caused a shift of beta2-adrenergic receptor mRNAs containing the 3'-untranslated region. Progressive 3'-terminal truncations of the receptor cDNA led to the identification of an AU-rich element at positions 329-337 of the 3'-untranslated region as the responsible cis-acting element. Substitution of this motif by cytosine residues almost completely abolished mRNA down-regulation and inhibited the formation of the RNA-protein complex. Even though the beta2-adrenergic receptor AU-rich element showed two U --> A transitions compared with the recently proposed AU-rich element consensus sequence, it revealed an almost identical destabilizing potency. Fusion of the beta2-adrenergic receptor 3'-untranslated region to the beta-globin coding sequence dramatically reduced the half-life of the chimeric transcript in an agonist- and cAMP-dependent manner. This suggests that the agonist-induced beta2-adrenergic receptor mRNA destabilization is regulated by cAMP-dependent RNA-binding protein(s) via a specific AU-rich element.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Danner, S. and Frank, M. and Lohse, M. J.}, biburl = {https://www.bibsonomy.org/bibtex/2eb230d6355f1a6706f4e4b58dfa05133/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {4a557b39b085851aed06e641c07760c1}, intrahash = {eb230d6355f1a6706f4e4b58dfa05133}, issn = {0021-9258 (Print) 0021-9258 (Linking)}, journal = {J Biol Chem}, keywords = {Adrenergic Animals Binding Cell Complementary Cricetinae DNA, Down-Regulation Fusion Globins/genetics Humans Line Messenger/*genetics Protein Proteins/genetics/metabolism RNA, RNA-Binding Recombinant beta-2/*agonists/genetics/metabolism beta-Agonists/*pharmacology Receptor}, month = {Feb 6}, note = {Danner, S Frank, M Lohse, M J Research Support, Non-U.S. Gov't United states The Journal of biological chemistry J Biol Chem. 1998 Feb 6;273(6):3223-9.}, number = 6, pages = {3223-9}, shorttitle = {Agonist regulation of human beta2-adrenergic receptor mRNA stability occurs via a specific AU-rich element}, timestamp = {2010-12-14T18:22:39.000+0100}, title = {Agonist regulation of human beta2-adrenergic receptor mRNA stability occurs via a specific AU-rich element}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9452435}, volume = 273, year = 1998 }