A model for the structure and functions of iron-responsive elements
Abstract
Most eukaryotic cells express two proteins, whose biosynthetic rates are determined by the intracellular iron status. The genes for both these proteins, ferritin and the transferrin receptor (TfR), are regulated at the post-transcriptional level, but by entirely different mechanisms. Ferritin mRNA levels are not affected by acute changes in iron availability. Ferritin biosynthesis is regulated translationally via a defined element contained within the 5' untranslated region (UTR) of the ferritin mRNA. This element has been highly conserved during evolution and has been termed an iron-responsive element (IRE). In contrast to ferritin, the regulation of TfR biosynthesis is mirrored by equivalent changes in TfR mRNA levels. The genetic information for this regulation is mostly located in the region of the gene encoding the 3' UTR of the TfR mRNA. Five elements that closely resemble the ferritin IRE are contained within the region which is critical for TfR regulation. The IRE is suggested to function by forming a specific stem-loop structure that interacts with a transacting factor in an iron-dependent fashion. We present a model that accommodates the mediation of distinct post-transcriptional regulatory phenomena via IREs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An IRE in the 5′ UTR of mRNA is also located in other genes involved in the regulation of iron levels in the cell, including ferritin (heavy and light chains) and eALAS.
“Such an IRE in the 5′ UTR of mRNA is also located in other genes involved in the regulation of iron levels in the cell, including ferritin (heavy and light chains) and eALAS, which is involved in heme synthesis in erythroid cells (see Fig. 2) (131).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [131]
Prototypical HH is characterized by progressive iron loading, particularly in the liver, heart, and pancreas.
“Prototypical HH is characterized by progressive iron loading, particularly in the liver, heart, and pancreas (131).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [131]
IRP has an important role in sensing iron levels and transmitting signals to regulate posttranscriptionally a number of important factors involved in iron management.
“IRP has an important role in the sensing of iron levels and transmission of signals to regulate posttranscriptionally a number of important factors involved in iron management (131).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [131]
The citation lists haven’t been fetched yet
References 30 · Cited by 116
- Authors
- Hentze, M. W., Caughman, S. W., Casey, J. L., Kodier, D. M., Rouault, T. A., Harford, J. B., & Klausner, R. D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Klausner, Richard D.
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 1988-12
- Volume
- 72
- Issue
- 1-2
- Pages
- 201-208
- ISSN
- 0378-1119 (ISSN-L)
- OpenAlex
- W2007078956
- Cited by
- 116
- References
- 30
- Citations by year
- 2025: 1 · 2023: 2 · 2021: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene (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, ferritin, transferrin receptor, post-transcriptional regulation, iron homeostasis, 5' untranslated region, 3' untranslated region, stem-loop structure, trans-acting factors, mRNA stability, translational regulation
- MeSH terms
- Animals, Base Sequence, Chickens, Ferritins, Gene Expression Regulation, Genes, Humans, Iron, Models, Genetic, Molecular Sequence Data, Nucleic Acid Conformation, Rana catesbeiana, Receptors, Transferrin, Sequence Homology, Nucleic Acid, Oligonucleotide Probes, Macromolecular Substances, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
