REGULATION OF CYTOSOLIC PROTEINS BINDING CIS-ELEMENTS IN THE 5' LEADER SEQUENCE OF THE ANGIOTENSIN AT(1) RECEPTOR MESSENGER-RNA

RNA binding proteins (BPs) have been identified which bind within a -2 71 to -174 nt domain in the 5' leader sequence (5'LS) of the rat type 1 angiotensin (AT(1)) receptor mRNA and which encompass RNA cis elemen ts upstream of -239. A 100 kDa RNA-protein complex is observed by UV-c rosslinking in several tissues including brain, lung, and spleen. 5'LS RNA transcripts of the 1a and 1b AT receptor subtypes are strong comp etitors of 5'LS-protein complex formation. In contrast, antisense 5'LS AT(1a) transcripts, plasmid transcripts, poly U and poly A RNAs, or 5 'LS AT(1a) cDNA are poor competitors. Deoxycorticosterone acetate (DOC A) decreased 5'LS-BP activities in the forebrain and hypothalamus unde r conditions known to significantly increase AT(1) receptor expression . DOCA had no effect on 5'LS-BP activities in the pituitary which corr elates with its lack of effect on pituitary AT(1) receptor expression. These results indicate that DOCA differentially regulates 5'LS-BP act ivities in a tissue-specific manner and suggest that physiologically m ediated changes in ATI receptor expression are mediated by alterations in 5'LS-BP activities, which represents a previously unrecognized lev el of regulation for the renin angiotensin system. (C) 1998 Academic P ress.