TY - JOUR
T1 - The inhibition of the iron responsive element RNA-protein interaction by heme does not mimic in vivo iron regulation
AU - Haile, D. J.
AU - Rouault, T. A.
AU - Harford, J. B.
AU - Klausner, R. D.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1990
Y1 - 1990
N2 - Hemin at > 1 μM concentrations inhibits the interaction of the iron responsive element (IRE) and the iron responsive element binding protein (IRE-BP) as measured by gel retardation and UV cross-linking. Heme has recently been proposed to inhibit the repression of translation of an IRE-containing mRNA (Lin, J.J., Daniels-McQueen, S., Patino, M.M., Gaffield, L., Walden, W.E., and Thach, R.E. (1990) Science 247, 74-76). Our binding inhibition provides structural support for these observations. The action of heme, however, does not mimic the physiologically demonstrated inhibition of high affinity binding of the IRE to IRE-BP by the oxidation of a sulfhydryl of the IRE-BP. In addition to this effect, hemin also inhibits a wide variety of RNA and DNA binding proteins, restriction endonucleases, and nucleases. Therefore, in vitro, the inhibitory effects of hemin are not limited to the interaction of the IRE-BP and the IRE, but are nonspecific and affect a wide variety of nucleic acid-protein interactions. Any hypothesis on the effects on protein-nucleic acid interactions employing > 1 μM concentrations of hemin should be interpreted with caution.
AB - Hemin at > 1 μM concentrations inhibits the interaction of the iron responsive element (IRE) and the iron responsive element binding protein (IRE-BP) as measured by gel retardation and UV cross-linking. Heme has recently been proposed to inhibit the repression of translation of an IRE-containing mRNA (Lin, J.J., Daniels-McQueen, S., Patino, M.M., Gaffield, L., Walden, W.E., and Thach, R.E. (1990) Science 247, 74-76). Our binding inhibition provides structural support for these observations. The action of heme, however, does not mimic the physiologically demonstrated inhibition of high affinity binding of the IRE to IRE-BP by the oxidation of a sulfhydryl of the IRE-BP. In addition to this effect, hemin also inhibits a wide variety of RNA and DNA binding proteins, restriction endonucleases, and nucleases. Therefore, in vitro, the inhibitory effects of hemin are not limited to the interaction of the IRE-BP and the IRE, but are nonspecific and affect a wide variety of nucleic acid-protein interactions. Any hypothesis on the effects on protein-nucleic acid interactions employing > 1 μM concentrations of hemin should be interpreted with caution.
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M3 - Article
C2 - 2376574
AN - SCOPUS:0025349992
VL - 265
SP - 12786
EP - 12789
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 22
ER -