The Germania of Tacitus.

Spine title: The Germania of Tacitus.Includes bibliographical references and indexes

Post-transcriptional regulation of soluble guanylyl cyclase expression in rat aorta

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

Subject matter of Tacitus Annals, I-III : including full index to persons and places /

"...a compilation culled from the larger Furneaux..."Mode of access: Internet

Neuronal HuD gene encoding a mRNA stability regulator is transcriptionally repressed by thyroid hormone

Many genes governed by thyroid hormone (T3) lack binding sites for its receptor (TR) and are thought to be post-transcriptionally regulated by T3. Here we demonstrate that the HuD gene, which encodes a neurone-specific protein that binds to mRNA and modulates its stability, is regulated by T3. HuD RNA and protein expression were strongly up-regulated in specific areas of the hypothyroid rat brain, and reduced by T3 in rat PC12 and mouse N2a cells containing appropriate TR levels. Furthermore, T3 inhibited the transcription of HuD in run-on assays. Finally, HuD protein bound with high affinity to two sequences in acetylcholinesterase mRNA, and ectopic HuD expression increased its abundance in N2a cells. This is the first report of a gene encoding an mRNA stability regulator that is under T3 control. The results suggest that HuD may mediate some T3 effects by altering the half-life of mRNAs for acetylcholinesterase and other genes.This work was supported by Grant SAF2001-2291 from Ministerio de Ciencia y Tecnología of Spain.Peer Reviewe