Regulation of Cytosolic Proteins BindingcisElements in the 5′ Leader Sequence of the Angiotensin AT1Receptor mRNA

Abstract

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 RNAciselements 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 AT1atranscripts, plasmid transcripts, poly U and poly A RNAs, or 5′LS AT1acDNA are poor competitors. Deoxycorticosterone acetate (DOCA) decreased 5′LS-BP activities in the forebrain and hypothalamus under conditions known to significantly increase AT1receptor expression. DOCA had no effect on 5′LS-BP activities in the pituitary which correlates with its lack of effect on pituitary AT1receptor expression. These results indicate that DOCA differentially regulates 5′LS-BP activities in a tissue-specific manner and suggest that physiologically mediated changes in AT1receptor expression are mediated by alterations in 5′LS-BP activities, which represents a previously unrecognized level of regulation for the renin angiotensin system.