A cis-acting element is necessary and sufficient for translational regulation of human ferritin expression in response to iron.
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Ferritin plays a key role in determining the intracellular fate of iron and is highly regulated by the iron status of the cell. We have identified a cis-acting element in the transcribed but nontranslated 5' leader sequence of human ferritin heavy-chain mRNA. In transiently transfected murine fibroblasts, the presence of a 157-nucleotide region of the 5' leader sequence was found to be necessary for iron-dependent regulation of ferritin biosynthesis. Further, this 5' leader region is sufficient to transfer iron-mediated translational control to the expression of a heterologous gene product, chloramphenicol acetyltransferase.
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In 1987, investigators observed that conserved sequences in the 5' UTRs of both H- and L-ferritin mRNAs were needed to control a ready but quiescent pool of ferritin mRNA.
“In 1987, investigators observed that conserved sequences in the 5Ј untranslated regions (UTRs) of both H-and L-ferritin mRNAs were needed to control a ready but quiescent pool of ferritin mRNA in the cell, which could quickly be mobilized to produce ferritin protein when iron was abundant.22,23”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [23]
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Cites
DNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572 · see citing works
A new technique for the assay of infectivity of human adenovirus 5 DNA
Graham, F. L., & van der Eb, A. J. (1973) · Virology · doi:10.1016/0042-6822(73)90341-3 · Cited by 9,734 · see citing works
Recombinant Genomes Which Express Chloramphenicol Acetyltransferase in Mammalian Cells
Gorman, C., Moffat, L. F., & Howard, B. H. (1982) · Molecular and Cellular Biology · doi:10.1128/mcb.2.9.1044 · Cited by 7,673 · see citing works
Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information
Zuker, M., & Stiegler, P. (1981) · Nucleic Acids Research · doi:10.1093/nar/9.1.133 · Cited by 3,604 · see citing works
Recombinant Genomes Which Express Chloramphenicol Acetyltransferase in Mammalian Cells
Gorman, C. M., Moffat, L. F., & Howard, B. H. (1982) · Molecular and Cellular Biology · doi:10.1128/mcb.2.9.1044-1051.1982 · Cited by 3,106 · see citing works
Iron Transport and Storage Proteins
Aisen, P., & Listowsky, I. (1980) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.49.070180.002041 · Cited by 1,179 · see citing works
Influences of mRNA secondary structure on initiation by eukaryotic ribosomes.
Kozak, M. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.9.2850 · Cited by 687 · see citing works
Multiple upstream AUG codons mediate translational control of GCN4
Mueller, P. P., & Hinnebusch, A. G. (1986) · Cell · doi:10.1016/0092-8674(86)90384-3 · Cited by 641 · see citing works
Ferritin: structure, biosynthesis, and role in iron metabolism.
Munro, H. N., & Linder, M. C. (1978) · Physiological Reviews · doi:10.1152/physrev.1978.58.2.317 · Cited by 404 · see citing works
Novel mechanism for translational control in regulation of ferritin synthesis by iron.
Zähringer, J., Baliga, B. S., & Munro, H. N. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.3.857 · Cited by 318 · see citing works
The preferential translation of Drosophila hsp70 mRNA requires sequences in the untranslated leader
McGarry, T. J., & Lindquist, S. L. (1985) · Cell · doi:10.1016/0092-8674(85)90286-7 · Cited by 289 · see citing works
Variation among human 28S ribosomal RNA genes.
Gonzalez, I. L., Gorski, J. L., Campen, T. J., Dorney, D. J., Erickson, J. M., Sylvester, J. E., & Schmickel, R. D. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.22.7666 · Cited by 288 · see citing works
Tyner, A. L., & Fuchs, E. V. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.5.1945 · Cited by 163 · see citing works
HAZARD, J. T., & Drysdale, J. W. (1977) · Nature · doi:10.1038/265755a0 · Cited by 161 · see citing works
Both subunits of rat liver ferritin are regulated at a translational level by iron induction
Aziz, N., & Munro, H. N. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.2.915 · Cited by 161 · see citing works
Structure of gene and pseudogenes of human apoferritin H
Costanzo, F. S., Colombo, M. P., Staempfli, S., Santoro, C., Marone, M., Frank, R., Delius, H., & Cortese, R. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.2.721 · Cited by 126 · see citing works
Thomas, G., & Thomas, G. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.6.2137 · Cited by 119 · see citing works
A cis-acting element within the 5′ leader of a cytomegalovirus β transcript determines kinetic class
Geballe, A. P., Spaete, R. R., & Mocarski, E. S. (1986) · Cell · doi:10.1016/0092-8674(86)90068-1 · Cited by 115 · see citing works
Chou, C. C., Gatti, R. A., Fuller, M. L., CONCANNON, P. J., Wong, A., Chada, S., Davis, R. C., & Salser, W. A. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.566 · Cited by 103 · see citing works
Translational control of ferritin synthesis by iron in embryonic reticulocytes of the bullfrog.
Shull, G. E., & Theil, E. C. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45363-5 · Cited by 102 · see citing works
Cloning of the gene coding for human L apoferritin
Santoro, C., Marone, M., Ferrone, M., Costanzo, F. S., Colombo, M., Minganti, C., Cortese, R., & Silengo, L. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.7.2863 · Cited by 101 · see citing works
Hemin, chelatable iron, and the regulation of transferrin receptor biosynthesis.
Rouault, T. A., Rao, K., Harford, J. B., et al. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38652-0 · Cited by 91 · see citing works
Self-citationCostanzo, F. S., Santoro, C., Colantuoni, V., Bensi, G., Raugei, G., Romano, V., & Cortese, R. (1984) · The EMBO Journal · doi:10.1002/j.1460-2075.1984.tb01756.x · Cited by 89 · see citing works
Hentze, M. W., Keim, S., Papadopoulos, P., O'Brien, S., Modi, W., Drysdale, J., Leonard, W. J., Harford, J. B., & Klausner, R. D. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.19.7226 · Cited by 79 · see citing works
Self-citationAbnormality in tissue isoferritin distribution in idiopathic haemochromatosis
Powell, L. W., Alpert, E., Isselbacher, K. J., & Drysdale, J. W. (1974) · Nature · doi:10.1038/250333a0 · Cited by 66 · see citing works
Isolation and characterization of a cDNA clone for human ferritin heavy chain.
Boyd, D. H., Jain, S. K., Crampton, J. M., et al. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.15.4751 · Cited by 50 · see citing works
Regulation of intracellular iron distribution in K562 human erythroleukemia cells.
Mattia, E. D., Josić, D., Ashwell, G., Klausner, R. E., & van Renswoude, J. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38542-3 · Cited by 49 · see citing works
Self-citationShull, G. E., & Theil, E. C. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)82005-5 · Cited by 46 · see citing works
Chou, C., Gatti, R. A., Fuller, M. L., et al. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.566-573.1986 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 7
- [8]Zahringer, J., Baliga, B. S. & Munro, H. N. (1976) Proc. Natl. Acad. Sci. USA 73, 857–861.
- [12]Boyd, D., Jain, S. K., Crampton, J., Barrett, K. J. & Drysdale, J. (1984) Proc. Natl. Acad. Sci. USA 81, 4751–4755.
- [13]Hentze, M. W., Keim, S., Papadopoulos, P., O'Brien, S., Modi, W., Drysdale, J., Leonard, W. J., Harford, J. B. & Klausner, R. D. (1986) Proc. Natl. Acad. Sci. USA 83, 7226-7231.
- [16]Rouault, T. A., Hentze, M. W., Dancis, A., Caughman, W., Harford, J. B. & Klausner, R. D. (1987) Proc. Natl. Acad. Sci. USA 84, in press.
- [17]Sanger, F., Nicklen, S. & Coulson, A. R. (1977) Proc. Natl. Acad. Sci. USA 74, 5463–5467.
- [25]Kozak, M. (1986) Proc. Natl. Acad. Sci. USA 83, 2850–2854.
- [28]Laudien Gonzales, I., Gorski, J. L., Campen, T. J., Dorney, D. J., Erickson, J. M., Sylvester, J. E. & Schmickel, R. D. (1985) Proc. Natl. Acad. Sci. USA 82, 7666–7670.
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Harrison, P. M., & Arosio, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00022-9 · Cited by 2,667 · see citing works
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Torti, F. M., & Torti, S. V. (2002) · Blood · doi:10.1182/blood.v99.10.3505 · Cited by 1,173 · see citing works
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Casey, J. L., Hentze, M. W., Koeller, D. M., Caughman, S. W., Rouault, T. A., Klausner, R. D., & Harford, J. B. (1988) · Science · doi:10.1126/science.2452485 · Cited by 709 · see citing works
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Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623 · see citing works
Hentze, M. W., Caughman, S. W., Rouault, T. A., Barriocanal, J. G., Dancis, A., Harford, J. B., & Klausner, R. D. (1987) · Science · doi:10.1126/science.3685996 · Cited by 571 · see citing works
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Thermann, R., Neu‐Yilik, G., Deters, A., Frede, U., Wehr, K., Hagemeier, C., Hentze, M. W., & Kulozik, A. E. (1998) · The EMBO Journal · doi:10.1093/emboj/17.12.3484 · Cited by 406 · see citing works
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Rouault, T. A., Hentze, M. W., Caughman, S. W., Harford, J. B., & Klausner, R. D. (1988) · Science · doi:10.1126/science.3413484 · Cited by 351 · see citing works
Self-citationTorti, S. V., Kwak, E. L., Miller, S. C., Miller, L. L., Ringold, G. M., Myambo, K. B., Young, A. P., & Torti, F. M. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37801-3 · Cited by 295 · see citing works
Gray, N. K., & Hentze, M. W. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06699.x · Cited by 276 · see citing works
Self-citationLiving 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
Sonntag, W. E., Lynch, C. D., Cefalu, W. T., Ingram, R. L., Bennett, S. A., Thornton, P. L., & Khan, A. S. (1999) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/54.12.b521 · Cited by 229 · see citing works
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Miller, L. L., Miller, S. C., Torti, S. V., Tsuji, Y., & Torti, F. M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.11.4946 · Cited by 213 · see citing works
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Fahmy, M., & Young, S. P. (1993) · Biochemical Journal · doi:10.1042/bj2960175 · Cited by 150 · see citing works
Goossen, B., Caughman, S. W., Harford, J. B., Klausner, R. D., & Hentze, M. W. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07635.x · Cited by 144 · see citing works
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Caughman, S. W., Hentze, M. W., Rouault, T. A., Harford, J. B., & Klausner, R. D. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37387-3 · Cited by 85 · see citing works
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- Authors
- Hentze, M. W., Rouault, T. A., Caughman, S. W., Dancis, A., Harford, J. B., & Klausner, R. D.
- Affiliations
- National Institutes of Health (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1987-10
- Volume
- 84
- Issue
- 19
- Pages
- 6730-6734
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC299157
- OpenAlex
- W2019914595
- Cited by
- 249
- References
- 29
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 4
- FWCI
- 14.18
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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
- ferritin, iron regulation, translational regulation, cis-regulatory elements, 5' leader sequence, iron-responsive element, chloramphenicol acetyltransferase, iron homeostasis
- MeSH terms
- Base Sequence, Cloning, Molecular, Ferritins, Gene Expression Regulation, Genes, Regulator, Humans, Iron, Plasmids, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis
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