ArticleProceedings of the National Academy of Sciences of the United States of America2012
Fe2+ binds iron responsive element-RNA, selectively changing protein-binding affinities and regulating mRNA repression and activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Review
- 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
- FeInternational journal of molecular sciences · 2025Article
- Iron-Mediated Overexpression of Amyloid Precursor Protein via Iron Responsive mRNA in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes.PLoS computational biology · 2025Article
- α-Synuclein Iron-Responsive-Element RNA and Iron Regulatory Protein Affinity Is Specifically Reduced by Iron in Parkinson's Disease.Biomolecules · 2025Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Iron responsive elements mRNA regulate Alzheimer's amyloid precursor protein translation through iron sensing.Frontiers in aging neuroscience · 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
- The role of structure in regulatory RNA elements.Bioscience reports · 2024Review
- Metals in Alzheimer's Disease.Biomedicines · 2023Review
- Iron response elements (IREs)-mRNA of Alzheimer's amyloid precursor protein binding to iron regulatory protein (IRP1): a combined molecular docking and spectroscopic approach.Scientific reports · 2023Article
- Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns.Journal of Zhejiang University. Science. B · 2022Review
- Reconsidering theACS bio & med chem Au · 2022Article
- Diverse functional elements in RNA predicted transcriptome-wide by orthogonal RNA structure probing.Nucleic acids research · 2021Article
- Iron enhances the binding rates and translational efficiency of iron responsive elements (IREs) mRNA with initiation factor eIF4F.PloS one · 2021Article
- Differential translational control of 5' IRE-containing mRNA in response to dietary iron deficiency and acute iron overload.Metallomics : integrated biometal science · 2020Article
- Defects in the rice aconitase-encoding OsACO1 gene alter iron homeostasis.Plant molecular biology · 2020Article
- 5'-UTR recruitment of the translation initiation factor eIF4GI or DAP5 drives cap-independent translation of a subset of human mRNAs.The Journal of biological chemistry · 2020Article
- Altered Iron Metabolism and Impact in Cancer Biology, Metastasis, and Immunology.Frontiers in oncology · 2020Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Iron increases synthesis rates of proteins encoded in iron-responsive element (IRE)-mRNAs; metabolic iron ("free," "labile") is Fe(2+). The noncoding IRE-RNA structure, approximately 30 nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. IRE-RNA riboregulators bind specifically to iron-regulatory proteins (IRP) proteins, inhibiting ribosome binding. Deletion of the IRE-RNA from an mRNA decreases both IRP binding and IRP-independent protein synthesis, indicating effects of other "factors." Current models of IRE-mRNA regulation, emphasizing iron-dependent degradation/modification of IRP, lack answers about how iron increases IRE-RNA/IRP protein dissociation or how IRE-RNA, after IRP dissociation, influences protein synthesis rates. However, we observed Fe(2+) (anaerobic) or Mn(2+) selectively increase the IRE-RNA/IRP K(D). Here we show: (i) Fe(2+) binds to the IRE-RNA, altering its conformation (by 2-aminopurine fluorescence and ethidium bromide displacement); (ii) metal ions increase translation of IRE-mRNA in vitro; (iii) eukaryotic initiation factor (eIF)4F binds specifically with high affinity to IRE-RNA; (iv) Fe(2+) increased eIF4F/IRE-RNA binding, which outcompetes IRP binding; (v) exogenous eIF4F rescued metal-dependent IRE-RNA translation in eIF4F-depeleted extracts. The regulation by metabolic iron binding to IRE-RNA to decrease inhibitor protein (IRP) binding and increase activator protein (eIF4F) binding identifies IRE-RNA as a riboregulator.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.