Identification of a conserved and functional iron-responsive element in the 5'-untranslated region of mammalian mitochondrial aconitase
Open accessAbstract
Iron-responsive elements (IREs) are RNA stem-loop motifs found in genes of iron metabolism. When cells are iron-depleted, iron regulatory proteins (IRPs) bind to IREs in the transcripts of ferritin, transferrin receptor, and erythroid amino-levulinic acid synthetase. Binding of IRPs to IRE motifs near the 5' end of the transcript results in attenuation of translation while binding to IREs in the 3'-untranslated region of the transferrin receptor results in protection from endonucleolytic cleavage. Iron deprivation results in activation of IRE binding activity, whereas iron replete cells lose IRE binding activation. Here, we report the identification of a conserved IRE in the 5'-untranslated region of the transcript of the citric acid cycle enzyme mitochondrial aconitase from four different mammalian species. The IRE in the transcript of mitochondrial aconitase can mediate in vitro translational repression of mitochondrial aconitase by IRPs. Furthermore, levels of mitochondrial aconitase are decreased in mice maintained on a low iron diet, whereas levels of mRNA remain unchanged. The decrease in levels of mitochondrial aconitase is likely due to activation of IRP binding and consequent attenuation of translation. Thus, expression of the iron-sulfur protein mitochondrial aconitase and function of the citric acid cycle may be regulated by iron levels in cells.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The 5′ end of ACO2 contains a conserved IRE, likely responsible for reduced ACO2 protein expression in mice on a low iron diet.
“The 5′ end of ACO2 contains a conserved IRE, which is likely responsible for the reduction in ACO2 protein expression observed in mice maintained on a low iron diet (152).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [152]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
On Finding All Suboptimal Foldings of an RNA Molecule
Zuker, M. (1989) · Science · doi:10.1126/science.2468181 · Cited by 2,023 · see citing works
Tam, J. P. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.15.5409 · Cited by 1,251 · see citing works
Dandekar, T., Stripecke, R., Gray, N. K., Goossen, B., Constable, A., Johansson, H. E., & Hentze, M. W. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07716.x · Cited by 347 · see citing works
Kennedy, M. C., Mende‐Mueller, L., Blondin, G. A., & Beinert, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.24.11730 · Cited by 341 · see citing works
Haile, D. J., Rouault, T. A., Tang, C., Chin, J., Harford, J. B., & Klausner, R. D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7536 · Cited by 270 · see citing works
Self-citationGuo, B., Yu, Y., & Leibold, E. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)51075-4 · Cited by 257 · see citing works
Samaniego, F., Chin, J., Iwaï, K., Rouault, T. A., & Klausner, R. D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47367-x · Cited by 219 · see citing works
Self-citationA regulated RNA binding protein also possesses aconitase activity.
Kaptain, S., Downey, W. E., Tang, C., Philpott, C. M., Haile, D. J., Orloff, D. G., Harford, J. B., Rouault, T. A., & Klausner, R. D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.22.10109 · Cited by 201 · see citing works
Self-citationHaile, D. J., Hentze, M. W., Rouault, T. A., Harford, J. B., & Klausner, R. D. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.11.5055-5061.1989 · Cited by 172 · see citing works
Self-citationGray, N. K., QUICK, S., Goossen, B., Constable, A., Hirling, H., Kühn, L. C., & Hentze, M. W. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb18420.x · Cited by 140 · see citing works
Kohler, S. A., Henderson, B. R., & Kühn, L. C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.51.30781 · Cited by 125 · see citing works
Differential Modulation of the RNA-binding Proteins IRP-1 and IRP-2 in Response to Iron
Henderson, B. R., & Kühn, L. C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.35.20509 · Cited by 95 · see citing works
An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein
Rouault, T. A., Haile, D. J., Downey, W. E., Philpott, C. C., Tang, C. K., Samaniego, F., Chin, J., Paul, I. A., Orloff, D. G., Harford, J. B., et al. (1992) · BioMetals · doi:10.1007/bf01061319 · Cited by 91 · see citing works
Self-citationEmery-Goodman, A., Hirling, H., Scarpellino, L., Henderson, B. R., & Kühn, L. C. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.6.1457 · Cited by 89 · see citing works
Kim, H., Klausner, R. D., & Rouault, T. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.4983 · Cited by 81 · see citing works
Self-citationTang, C., Chin, J., Harford, J. B., Klausner, R. D., & Rouault, T. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35789-2 · Cited by 73 · see citing works
Self-citationZheng, L., Kennedy, M. C., Blondin, G. A., Beinert, H., & Zalkin, H. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90287-7 · Cited by 72 · see citing works
Iron regulatory factor — the conductor of cellular iron regulation
Melefors, Ö., & Hentze, M. W. (1993) · Blood Reviews · doi:10.1016/0268-960x(93)90012-s · Cited by 72 · see citing works
Cloning and structural characterization of porcine heart aconitase.
Zheng, L., Andrews, P., Hermodson, M. A., Dixon, J. E., & Zalkin, H. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39874-6 · Cited by 68 · see citing works
Au, H. C., Ream-Robinson, D., Bellew, L. A., Broomfield, P. L. E., Saghbini, M., & Scheffler, I. E. (1995) · Gene · doi:10.1016/0378-1119(95)00162-y · Cited by 51 · see citing works
Basilion, J. P., Kennedy, M. C., Beinert, H., et al. (1994) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1994.1270 · Cited by 41 · see citing works
1 Molecular regulation of iron proteins
Kühn, L. C. (1994) · Baillière s Clinical Haematology · doi:10.1016/s0950-3536(05)80123-4 · Cited by 37 · see citing works
Beaumont, C., Seyhan, A., Yachou, A. K., Grandchamp, B., & Jones, R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31988-9 · Cited by 33 · see citing works
Regulation of ferritin H-chain expression in differentiating Friend leukemia cells
Coccia, E. M., Stellacci, E., Orsatti, R., Testa, U., & Battistini, A. (1995) · Blood · doi:10.1182/blood.v86.4.1570.bloodjournal8641570 · Cited by 23 · see citing works
Au, H. C., & Scheffler, I. E. (1994) · Gene · doi:10.1016/0378-1119(94)90158-9 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Kaptain, S., Downey, W. E., Tang, C., Philpott, C. C., Haile, D. J., Orloff, D. G., Harford, J. B., Rouault, T. A. & Klausner, R. D. (1991) Proc. Natl. Acad. Sci.
- Haile, D. J., Rouault, T. A., Tang, C. K., Chin, J., Harford, J. B. & Klausner, R. D. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 7536 -7540
- Kennedy, M. C., Mende-Mueller, L., Blondin, G. A. & Beinert, H. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 11730 -11734
- Tam, J. P. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 5409 -5413
- Rouault, T. A., and Klausner, R. D. (1996) Curr. Top. Cell. Regul. 35, in press
Cited by
Sorted by citations
The role of iron regulatory proteins in mammalian iron homeostasis and disease
Rouault, T. A. (2006) · Nature Chemical Biology · doi:10.1038/nchembio807 · Cited by 1,055 · see citing works
Chemistry and biology of eukaryotic iron metabolism
Aisen, P. (2001) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00063-2 · Cited by 804 · see citing works
Mitochondrial disease in superoxide dismutase 2 mutant mice
Melov, S., Coskun, P., Patel, M., Tuinstra, R., Cottrell, B., Jun, A. S., Zastawny, T. H., Dizdaroglu, M., Goodman, S. I., Huang, T.-T., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.3.846 · Cited by 581 · see citing works
Regulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535 · see citing works
“The 50 end of ACO2 contains a conserved IRE, which is likely responsible for the reduction in ACO2 protein expression observed in mice maintained on a low iron diet (152).”
BackgroundLaVaute, T., Smith, S., Cooperman, S., Iwai, K., Land, W., Meyron-Holtz, E., Drake, S. K., Miller, G., Abu-Asab, M., Tsokos, M., et al. (2001) · Nature Genetics · doi:10.1038/84859 · Cited by 509 · see citing works
Self-citationMammalian iron metabolism and its control by iron regulatory proteins
Anderson, C. P., Shen, M., Eisenstein, R. S., & Leibold, E. A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.05.010 · Cited by 493 · see citing works
Oexle, H., Gnaiger, E., & Weiss, G. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00088-2 · Cited by 307 · see citing works
The Role of Iron Regulation in Immunometabolism and Immune-Related Disease
Cronin, S. J. F., Woolf, C. J., Weiss, G., & Penninger, J. M. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00116 · Cited by 299 · see citing works
Molecular control of vertebrate iron homeostasis by iron regulatory proteins
Wallander, M. L., Leibold, E. A., & Eisenstein, R. S. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.05.004 · Cited by 287 · see citing works
Living with Iron (and Oxygen): Questions and Answers about Iron Homeostasis
Theil, E. C., & Goss, D. J. (2009) · Chemical Reviews · doi:10.1021/cr900052g · Cited by 265 · see citing works
Cooperman, S. S., Meyron-Holtz, E. G., Olivierre-Wilson, H., Ghosh, M. C., McConnell, J. P., & Rouault, T. A. (2005) · Blood · doi:10.1182/blood-2004-12-4703 · Cited by 235 · see citing works
Self-citationAllerson, C. R., Cazzola, M., & Rouault, T. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.37.26439 · Cited by 122 · see citing works
Self-citationMetabolic enzymes that bind RNA: yet another level of cellular regulatory network?
Cieśla, J. (2006) · Acta Biochimica Polonica · doi:10.18388/abp.2006_3360 · Cited by 106 · see citing works
- Authors
- Kim, H.-Y., LaVaute, T., Iwai, K., Klausner, R. D., & Rouault, T. A.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-09
- Volume
- 271
- Issue
- 39
- Pages
- 24226-24230
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2040420376
- Cited by
- 141
- References
- 25
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 4 · 2012: 2
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- 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 › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- iron-responsive element, iron regulatory proteins, mitochondrial aconitase, 5' untranslated region, protein synthesis inhibition, iron metabolism, iron-sulfur proteins, TCA cycle, low-iron diet
- MeSH terms
- Aconitate Hydratase, Animals, Binding, Competitive, Cattle, Humans, Iron, Iron-Sulfur Proteins, Mitochondria, Repressor Proteins, RNA, Messenger, Swine, Protein Biosynthesis, Gene Expression Regulation, Enzymologic, Consensus Sequence, RNA-Binding Proteins, Iron-Regulatory Proteins, Mice
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
