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The IRE Model for Families of RNA Structures

Selective Recognition by Binding Proteins (IRPs), NMR Spectroscopy and Probing with Metal Coordination Complexes

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RNA Biochemistry and Biotechnology

Part of the book series: NATO Science Series ((ASHT,volume 70))

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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].

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References

  1. 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

    Google Scholar 

  2. 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.

    Article  CAS  Google Scholar 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. Andrews, N.C., and Levy, J., (1998), Iron is hot: An update on the pathophysiology of hemochromatosis, BLOOD 92, 1845–1851.

    PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    PubMed  CAS  Google Scholar 

  9. 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.

    PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. Jenison, R.D., Gill, S.C., Pardi, A., and Polisky, B., (1994), High-Resolution Molecular Discrimination by RNA, Science 263, 1425–1429.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  CAS  Google Scholar 

  20. 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.

    Article  CAS  Google Scholar 

  21. 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.

    Google Scholar 

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© 1999 Springer Science+Business Media Dordrecht

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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

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  • 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

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