Abstract
Regulation of mRNA is likely an ancient form of genetic control, with the current rapid expansion of knowledge driven by advances in biotechnology. The regulation of ferritin mRNA by iron in animals, an older example of mRNA regulation, has been extended to other mRNAs of iron and oxidative metabolism. The regulatory element (IRE) is conserved in animal mRNAs encoding the transferrin receptor (TfR), m-aconitase, erythroid aminolevulinate synthase (eALAS) and Nramp2 (an ion transport protein), as well as ferritin. [1–4]. [The sequence identity of an IRE is >95% in the mRNAs of different animals, but is only 36–60% among different IRE containing mRNAs in the same animal]. An IRE can regulate either mRNA ribosome binding (translation) or degradation (stability/turnover). Control of ribosome binding is the mechanism of IRE-dependent regulation for ferritin, eALAS synthesis and m-aconitase, while control of nuclease binding/activity appears to be the mechanism of IRE-dependent regulation for TfR and Nramp2 synthesis. A common secondary structure is shared among the isoIREs which includes a hairpin loop (CAGUGX) and a base paired stem with an interruption or “hinge” in mid-stem. Stem base pair sequence is mRNA-specific as is the structure of the “hinge”. Among iso-IREs, the greatest variation occurs in the lower stem [1].
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Theil, E.C., (1998) The Iron Responsive Element (IRE) Family of mRNA Regulators,Regulation of Iron Transport and Uptake Compared in Animals, Plants, and Microorganisms IN: Metal Ions in Biological Systems, A. Sigel and Sigel, H. (Eds.), Marcel Dekker, Inc., New York, Vol. 35, pp. 403–434
Rouault, T.A., and Klausner, R.D., (1996), Post-transcriptional regulation of genes of iron metabolism in mammalian cells, J. Biol. Inorg. Chem. 1, 494–499.
Hentze, M.W., and Kuhn, L.C., (1996), Molecular control of vertebrate iron metabolism: mRNAbased regulatory circuits operated by iron, nitric oxide, and oxidative stress, Proc. Natl. Acad. Sci. USA 93, 8175–8182.
Andrews, N.C., and Levy, J., (1998), Iron is hot: An update on the pathophysiology of hemochromatosis, BLOOD 92, 1845–1851.
Rouault, T.A., Stout, C.D., Kaptain, S., Harford, J.B., and Klausner, R.D., (1991), Structural Relationship between an Iron-Regulated RNA-Binding Protein (IRE-BP) and Aconitase: Functional Implications, Cell 64, 881–883.
Samaniego, F., Chin, J., Iwai, K., Rouault, T.A., and Klausner, R.D., (1994), Molecular Characterization of a Second Iron-responsive Element Binding Protein, Iron Regulatory Protein 2: Structure, Function, and Post-translational Regulation, Biological Chemistry 269, 30904–30910.
Guo, B., Brown, F.M., Phillips, J.D., Yu, Y., and Leibold, E.A., (1995), Characterization and Expression of Iron Regulatory Protein 2 (IRP2). Presence of Multiple IRP2 Transcripts Regulated by Intracellular Iron Levels, J. Biol. Chem. 270, 16529–16535.
Pantopoulos, K., Gray, N.K., and Hentze, M.W., (1995), Differential regulation of two related RNA-binding proteins, iron regulatory protein IRPA and IRPB, RNA 1, 155–163.
Iwai, K., Klausner, R.D., and Rouault, T.A., (1995), Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2, EMBO J 14, 5350–5357.
Haile, D.J., Rouault, T.A., Tang, C.K., Chin, J., Harford, J.B., and Klausner, R.D., (1992), Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: Role of the iron-sulfur cluster Proc. Natl. Acad. Sci. USA 89, 7536–7540.
Zheng, L., Kennedy, M.C., Blondin, G.A., Beinert, H., and Zalkin, H., (1992), Binding of Cytosolic Aconitase to the Iron Responsive Element of Porcine Mitochondrial Aconitase mRNA Arch. of Biochem. and Biophys. 299, 356–360.
Kim, H.-Y., LaVaute, T., Iwai, K., Klausner, R.D., andRouault, T.A., (1996), Identification of a Conserved and Functional Iron-responsive Element in the 5’-Untranslated Region of Mammalian Mitochondrial Aconitase, J. Biol. Chem. 271, 24226–24230.
Gray, N.K., Pantopoulos, K., Dandekar, T., Ackrell, B.A.C., and Hentze, M.W., (1996), Translational regulation of mammalian and Drosophila citric acid cycle enzymes via iron-responsive elements, Proc. Natl. Acad. Sci. USA 93, 4925–4930.
O.S. Chen, Schalinske, K.L. and Eisenstein, R.S., (1997), Dietary Iron Intake Modulates the Activity of Iron Regulatory Proteins and the Abundance of Ferritin and Mitochondrial Aconitase in Rat Liver, J. Nutrition 238–248.
Ke, Y., Wu, J., Leibold, E.A., Walden, W.E., and Theil, E.C., (1998), Loops and Bulge/Loops in Iron-responsive Element Isoforms Influence Iron Regulatory Protein Binding Journal of Biological Chemistry 273, 23637–23640.
Gdaniec, Z., Sierzputowska-Gracz, H., and Theil, E.C., (1998), Iron Regulatory Element and Internal Loop/Bulge Structure for Ferritin mRNA Studied by Cobalt(III) Hexammine Binding, Molecular Modeling, and NMR Spectroscopy, Biochemistry 37, 1505–1512.
Addess, K.J., Basilion, J.P., Klausner, R.D., Rouault, T.A., and Pardi, A., (1997), Structure and Dynamics of the Iron Responsive Element RNA: Implications for Binding of the RNA by Iron Regulatory Binding Proteins, J. Mol. Biol. 274, 72–83.
Jenison, R.D., Gill, S.C., Pardi, A., and Polisky, B., (1994), High-Resolution Molecular Discrimination by RNA, Science 263, 1425–1429.
Wang, Y.-H., Sczekan, S.R., Theil, E.C., (1990), Structure of the 5’ untranslated regulatory region of ferritin mRNA studied in solution, Nuc. Acids Res. 18, 4463–4468.
Thorp, H.H., McKenzie, R.A., Lin, P.-N., Walden, W.E., and Theil, E.C., (1996), Cleavage of functionally relevant sites in ferritin mRNA by oxidizing metal complexes, Inorganic Chemistry 35, 2773–2779.
Cliftan, S.A., Theil, E C., and Thorp, H. H., (1998), Oxidation of Guanines in the Iron Responsive Element RNA: Similar Structures from Chemical Modification and Recent NMR Studies, Chemistry and Biology in press.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Theil, E.C., Ke, Y., Gdaniec, Z., Sierzputowska-Gracz, H. (1999). The IRE Model for Families of RNA Structures. In: Barciszewski, J., Clark, B.F.C. (eds) RNA Biochemistry and Biotechnology. NATO Science Series, vol 70. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4485-8_18
Download citation
DOI: https://doi.org/10.1007/978-94-011-4485-8_18
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-7923-5862-6
Online ISBN: 978-94-011-4485-8
eBook Packages: Springer Book Archive