K. Krishnamurthi et al., REGULATION OF CYTOSOLIC PROTEINS BINDING CIS-ELEMENTS IN THE 5' LEADER SEQUENCE OF THE ANGIOTENSIN AT(1) RECEPTOR MESSENGER-RNA, Biochemical and biophysical research communications, 245(3), 1998, pp. 865-870
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.