Related Experiment Video
Updated: Aug 1, 2026
07:21
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Angiotensinogen messenger RNA stabilization by angiotensin II
C P Klett1, M P Printz, M Bader
1Department of Pharmacology, University of California at San Diego, La Jolla 92093-0636, USA.
Summary
Angiotensin II stabilizes angiotensinogen mRNA through a specific protein interaction in the 3' untranslated region. Genetic mutations affecting this binding can alter mRNA stability and impact angiotensinogen secretion, potentially contributing to hypertension.
Area of Science:
- Molecular Biology
- Genetics
- Cardiovascular Research
Background:
- Angiotensin II plays a crucial role in regulating blood pressure.
- The stability of angiotensinogen mRNA is a key factor in angiotensin II production.
- A polysomal stabilizing protein has been previously identified that binds to angiotensinogen mRNA.
Purpose of the Study:
- To elucidate the molecular mechanism by which angiotensin II stabilizes angiotensinogen mRNA.
- To investigate the role of a specific polysomal protein in this stabilization process.
- To explore the significance of these interactions in the context of rodent genetic hypertension.
Main Methods:
- Binding studies using partial and mutagenized sequences of the angiotensinogen 3' untranslated region (UTR).
- Analysis of angiotensinogen mRNA half-life in a cell-free system.
- Protein/RNA interaction determination via band shift assays.
- Polymerase chain reaction (PCR) cloning and sequencing of 3' UTR DNA.
- Site-directed mutagenesis to introduce specific point mutations.
Main Results:
- The 12,000 molecular weight polysomal protein specifically binds to the angiotensinogen 3' UTR, increasing mRNA half-life 10-fold.
- A G to C point mutation in the SHR 3' UTR significantly enhanced protein binding and mRNA half-life.
- Deletion of a U-rich sequence (UCCUU) in the 3' UTR abolished protein binding, identifying it as part of the binding motif.
Conclusions:
- Angiotensin II regulates hepatic angiotensinogen synthesis by inhibiting mRNA degradation via a polysomal protein.
- Mutations in the angiotensinogen 3' UTR can alter protein binding and mRNA stability.
- These alterations in mRNA half-life may significantly impact angiotensinogen secretion rates and contribute to hypertension.
Related Concept Videos
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
02:23RNA Editing
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
02:51mRNA Stability and Gene Expression
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
01:23Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...