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An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein

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Abstract

Post-transcriptional regulation of genes important in iron metabolism, ferritin and the transferrin receptor (TfR), is achieved through regulated binding of a cytosolic protein, the iron-responsive element binding protein (IRE-BP), to RNA stem-loop motifs known as iron-responsive elements (IREs). Binding of the IRE-BP respresses ferritin translation and represses degradation of the TfR mRNA. The IRE-BP senses iron levels and accordingly modifies binding to IREs through a novel sensing mechanism. An iron-sulfur cluster of the IRE-BP reversibly binds iron; when cytosolic iron levels are depleted, the cluster becomes depleted of iron and the IRE-BP acquires the capacity to bind IREs. When cytosolic iron levels are replete, the IRE-BP loses RNA binding capacity, but acquires enzymatic activity as a functional aconitase. RNA binding and aconitase activity are mutually exclusive activities of the IRE-BP, and the state of the iron-sulfur cluster determines how the IRE-BP will function.

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Authors and Affiliations

  1. Cell Biology and Metabolism Branch, National Institute of Child Health & Human Development, National Institutes of Health, Building 18, 20892, Bethesda, MD, USA

    Tracey A. Rouault, David J. Haile, William E. Downey, Caroline C. Philpott, Careen Tang, Felipe Samaniego, Jean Chin, Ian Paul, David Orloff, Joe B. Harford & Richard D. Klausner

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  1. Tracey A. Rouault
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  2. David J. Haile
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  3. William E. Downey
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  4. Caroline C. Philpott
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  5. Careen Tang
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  6. Felipe Samaniego
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  7. Jean Chin
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  8. Ian Paul
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  9. David Orloff
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  10. Joe B. Harford
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  11. Richard D. Klausner
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Rouault, T.A., Haile, D.J., Downey, W.E. et al. An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein. Biometals 5, 131–140 (1992). https://doi.org/10.1007/BF01061319

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  • DOI: https://doi.org/10.1007/BF01061319

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