Molecular characterization of a second iron-responsive element binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation.
Several genes critical to the uptake, sequestration, and utilization of iron are regulated at the post-transcriptional level. The mRNAs encoded by these genes contain highly conserved stem-loop structures called iron-responsive elements (IREs). IREs function as the nucleic acid-binding sites for a cytosolic RNA-binding protein called the IRE-binding protein or IRE-BP. Binding of the IRE-BP to IREs is reversibly regulated by the iron status of the cell. The IRE-BP is highly conserved among human, rat, mouse, and rabbit, and it is identical to the cytosolic form of aconitase. In this study, we demonstrate that a distinct human gene encoding a protein which is 57% identical to the initially described IRE-BP, now referred to as iron regulatory protein 1 or IRP1, is also capable of binding to IREs with the same in vitro affinity and specificity the originally identified protein. This second gene product, which we call IRP2, is expressed in many tissues, but its mRNA abundance and tissue distribution are different from IRP1. In most cell lines tested, levels of IRP2 are inversely regulated by iron levels due to iron-dependent regulation of the half-life of the protein. In addition to changes in total amounts of IRP2, we demonstrate that the IRE binding activity of IRP2 can also vary up to 4-fold in the absence of any change in IRP2 protein levels. The possible reasons for the existence of a second IRP are discussed.
Samaniego
F
F
Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892.
Chin
J
J
Iwai
K
K
Rouault
T A
TA
Klausner
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D035925:Iron-Regulatory Proteins; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D035925:Iron-Regulatory Proteins; D016601:RNA-Binding Proteins; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2