Regulation of cytosolic proteins binding cis elements in the 5' leader sequence of the angiotensin AT1 receptor mRNA.
RNA binding proteins (BPs) have been identified which bind within a -271 to -174 nt domain in the 5' leader sequence (5'LS) of the rat type 1 angiotensin (AT1) receptor mRNA and which encompass RNA cis elements upstream of -239. A 100 kDa RNA-protein complex is observed by UV-crosslinking in several tissues including brain, lung, and spleen. 5'LS RNA transcripts of the 1a and 1b AT receptor subtypes are strong competitors of 5'LS-protein complex formation. In contrast, antisense 5'LS AT1a transcripts, plasmid transcripts, poly U and poly A RNAs, or 5'LS AT1a cDNA are poor competitors. Deoxycorticosterone acetate (DOCA) decreased 5'LS-BP activities in the forebrain and hypothalamus under conditions known to significantly increase AT1 receptor expression. DOCA had no effect on 5'LS-BP activities in the pituitary which correlates with its lack of effect on pituitary AT1 receptor expression. These results indicate that DOCA differentially regulates 5'LS-BP activities in a tissue-specific manner and suggest that physiologically mediated changes in AT1 receptor expression are mediated by alterations in 5'LS-BP activities, which represents a previously unrecognized level of regulation for the renin angiotensin system.
Krishnamurthi
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K
Department of Medicine, Georgetown University Medical Center, Washington, DC 20007-2145, USA.
Zheng
W
W
Verbalis
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AD
Sandberg
K
K
D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D014018:Tissue Distribution
D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin