ArticleProceedings of the National Academy of Sciences of the United States of America2006
The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Small-Molecule Targeting of the Iron-Responsive Element in the APP mRNA 5'-UTR to Control Amyloid Translation in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Predicting small molecule-RNA interactions without RNA tertiary structures.Nature biotechnology · 2026Article
- Iron-Mediated Overexpression of Amyloid Precursor Protein via Iron Responsive mRNA in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Targeting Iron Responsive Elements (IREs) of APP mRNA into Novel Therapeutics to Control the Translation of Amyloid-β Precursor Protein in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022Review
- Understanding the characteristics of nonspecific binding of drug-like compounds to canonical stem-loop RNAs and their implications for functional cellular assays.RNA (New York, N.Y.) · 2021Article
- Iron enhances the binding rates and translational efficiency of iron responsive elements (IREs) mRNA with initiation factor eIF4F.PloS one · 2021Article
- Iron-responsive-like elements and neurodegenerative ferroptosis.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Review
- Targeting the Iron-Response Elements of the mRNAs for the Alzheimer's Amyloid Precursor Protein and Ferritin to Treat Acute Lead and Manganese Neurotoxicity.International journal of molecular sciences · 2019Review
- Small molecule alteration of RNA sequence in cells and animals.Bioorganic & medicinal chemistry letters · 2018Article
- Rapid kinetics of iron responsive element (IRE) RNA/iron regulatory protein 1 and IRE-RNA/eIF4F complexes respond differently to metal ions.Nucleic acids research · 2014Article
- Ferritin: the protein nanocage and iron biomineral in health and in disease.Inorganic chemistry · 2013Review
- Article
- RNA-Pt adducts following cisplatin treatment of Saccharomyces cerevisiae.ACS chemical biology · 2012Article
- Iron responsive mRNAs: a family of Fe2+ sensitive riboregulators.Accounts of chemical research · 2011Article
- The alpha-synuclein 5'untranslated region targeted translation blockers: anti-alpha synuclein efficacy of cardiac glycosides and Posiphen.Journal of neural transmission (Vienna, Austria : 1996) · 2011Article
- Nature of guanine oxidation in RNA via the flash-quench technique versus direct oxidation by a metal oxo complex.Inorganic chemistry · 2010Article
- Interaction of anthracyclines with iron responsive element mRNAs.Nucleic acids research · 2008Article
- Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide.Biochemical and biophysical research communications · 2008Article
- Ferritins: iron/oxygen biominerals in protein nanocages.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2006Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The binding of small molecules to distinctive three-dimensional structures in mRNA provides a new dimension in RNA control, previously limited to the targeting of secondary structures with antisense and RNA interference; such targeting can modulate mRNA function and rates of protein biosynthesis. Small molecules that selectively bind the iron-responsive element (IRE), a specific three-dimensional structure in the noncoding region of the ferritin mRNA model that is recognized by the iron-regulatory protein repressor, were identified by using chemical footprinting. The assay used involved an oxoruthenium(IV) complex that oxidizes guanine bases in RNA sequences. Small molecules that blocked oxidation of guanines in the internal loop region were expected to selectively increase the rate of ferritin synthesis, because the internal loop region of the ferritin IRE is distinctive from those of other IREs. The natural product yohimbine was found (based on gel mobility shifts) to block cleavage of the internal loop RNA site by >50% and seemed to inhibit protein binding. In the presence of yohimbine, the rate of biosynthesis of ferritin in a cell-free expression system (rabbit reticulocyte lysate) increased by 40%. Assignment of the IRE-yohimbine interaction as the origin of this effect was supported by a similar increase in synthesis of luciferase protein in a chimera of the IRE and luciferase gene. The identification of a small, drug-like molecule that recognizes a naturally occurring three-dimensional mRNA structure and regulates protein biosynthesis rates raises the possibility that small molecules can regulate protein biosynthesis by selectively binding to mRNA.
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