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Science 21 April 1989:
Vol. 244. no. 4902, pp. 357 - 359
DOI: 10.1126/science.2711187
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Articles

Science, Vol 244, Issue 4902, 357-359
Copyright © 1989 by American Association for the Advancement of Science

articles

Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction

MW Hentze, TA Rouault, JB Harford, and RD Klausner

Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.

Iron-responsive elements (IREs) are RNA motifs that have been identified within the 5' untranslated region of ferritin messenger RNA and the 3' untranslated region of transferrin receptor mRNA. A single IRE mediates iron-dependent control of ferritin translation, whereas multiple IREs are found in the region of the transferrin receptor mRNA responsible for iron-dependent control of mRNA stability. A cytosolic protein binds in vitro to the IREs of both mRNAs. The IRE-binding protein (IRE-BP) is shown to require free sulfhydryl groups for its specific interaction with the IRE. Treatment of lysates with reducing agents increases the binding activity, whereas agents that block sulfhydryls inhibit binding. Iron starvation, leading to decreased ferritin translation, results in increased binding activity, which is explained by an increase in the fraction of the IRE-BP that is in a fully reduced state.


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