Iron-Responsive Elements: Regulatory RNA Sequences That Control mRNA Levels and Translation
Abstract
The biosynthetic rates for both the transferrin receptor (TfR) and ferritin are regulated by iron. An iron-responsive element (IRE) in the 5′ untranslated portion of the ferritin messenger RNA (mRNA) mediates iron-dependent control of its translation. In this report the 3′ untranslated region of the mRNA for the human TfR was shown to be necessary and sufficient for iron-dependent control of mRNA levels. Deletion studies identified a 678-nucleotide fragment of the TfR complementary DNA that is critical for this iron regulation. Five potential stem-loops that resemble the ferritin IRE are contained within the region critical for TfR regulation. Each of two of the five TfR elements was independently inserted into the 5′ untranslated region of an indicator gene transcript. In this location they conferred iron regulation of translation. Thus, an mRNA element has been implicated in the mediation of distinct regulatory phenomena dependent on the context of the element within the transcript.
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Thermodynamic predictions indicated that the UTR sequences could form stable RNA hairpins with a characteristic secondary structure, termed iron responsive elements (IREs).
“Thermodynamic predictions indicated that the UTR sequences could form stable RNA hairpins with a characteristic secondary structure, termed iron responsive (or regulatory) elements (IREs).24”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [24]
Levels of accumulation of iron in the striatum of rhesus monkeys were positively correlated with aging-related motor deficits.
“Levels of accumulation of iron in the striatum of rhesus monkeys were positively correlated with aging-related motor deficits (42).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [42]
Monkeys exhibited age-related declines in motor function and dopamine release in the striatum, whereas iron concentration in the striatum increased.
“Monkeys exhibited age-related declines in motor function and dopamine release in the striatum, whereas iron concentration in the striatum increased.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [42]
Iron content was the best predictor of motor deficit.
“Iron content was the best predictor of motor deficit (42).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [42]
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- Authors
- Casey, J. L., Hentze, M. W., Koeller, D. M., Caughman, S. W., Rouault, T. A., Klausner, R. D., & Harford, J. B.
- Affiliations
- National Institutes of Health (US)
- Venue
- Science
- Published
- 1988-05-13
- Volume
- 240
- Issue
- 4854
- Pages
- 924-928
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1999347013
- Cited by
- 709
- References
- 31
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 10 · 2023: 14 · 2022: 8 · 2021: 15 · 2020: 6 · 2019: 6 · 2018: 15 · 2017: 6 · 2016: 12 · 2015: 9 · 2014: 16 · 2013: 11 · 2012: 11
- FWCI
- 31.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- iron-responsive element, transferrin receptor, ferritin, iron regulation, mRNA stability, translational regulation, 3' untranslated region, 5' untranslated region, stem-loop structure, post-transcriptional regulation, iron homeostasis
- MeSH terms
- Animals, Base Sequence, DNA, DNA, Recombinant, Ferritins, Humans, Iron, Plasmids, Receptors, Transferrin, Regulatory Sequences, Nucleic Acid, RNA, RNA, Messenger, Growth Hormone, Transcription, Genetic, Transfection, Transformation, Genetic, Protein Biosynthesis, Mice
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