TY  - JOUR
A1  - Klöß, Stephan
A1  - Furneaux, Henry
A1  - Mülsch, Alexander
T1  - Post-transcriptional regulation of soluble guanylyl cyclase expression in rat aorta
T2  - Journal of biological chemistry
N2  - We investigated the molecular mechanism of cyclic GMP-induced down-regulation of soluble guanylyl cyclase expression in rat aorta. 3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), an allosteric activator of this enzyme, decreased the expression of soluble guanylyl cyclase α1 subunit mRNA and protein. This effect was blocked by the enzyme inhibitor 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b-1,4)oxazin-1-one (NS2028) and by actinomycin D. Guanylyl cyclase α1mRNA-degrading activity was increased in protein extracts from YC-1-exposed aorta and was attenuated by pretreatment with actinomycin D and NS2028. Gelshift and supershift analyses using an adenylate-uridylate-rich ribonucleotide from the 3′-untranslated region of the α1 mRNA and a monoclonal antibody directed against the mRNA-stabilizing protein HuR revealed HuR mRNA binding activity in aortic extracts, which was absent in extracts from YC-1-stimulated aortas. YC-1 decreased the expression of HuR, and this decrease was prevented by NS2028. Similarly, down-regulation of HuR by RNA interference in cultured rat aortic smooth muscle cells decreased α1 mRNA and protein expression. We conclude that HuR protects the guanylyl cyclase α1 mRNA by binding to the 3′-untranslated region. Activation of guanylyl cyclase decreases HuR expression, inducing a rapid degradation of guanylyl cyclase α1 mRNA and lowering α1 subunit expression as a negative feedback response.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76089
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-760896
SN  - 0021-9258
VL  - 278
IS  - 4
SP  - 2377
EP  - 2383
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -