Differential regulation of two related RNA-binding proteins, iron regulatory protein (IRP) and IRPB - PubMed (original) (raw)
Differential regulation of two related RNA-binding proteins, iron regulatory protein (IRP) and IRPB
K Pantopoulos et al. RNA. 1995 Apr.
Abstract
The iron regulatory protein (IRP) is a cytoplasmic RNA-binding protein that regulates cellular iron metabolism at the posttranscriptional level. IRP is an unusual bifunctional molecule: in iron-replete cells it predominantly exists as a 4Fe-4S protein and exhibits aconitase enzymatic activity, whereas apo-IRP prevails in iron-starved cells and binds to iron-responsive elements (IREs), structural motifs within the untranslated regions of mRNAs involved in iron metabolism. A related protein with iron-regulated IRE-binding activity, IRPB, was previously identified in rodent cells. IRE-binding by IRP and IRPB is induced by iron deprivation and nitric oxide (NO). Controversial hypotheses have proposed that the induction of IRE-binding activity by iron results either from de novo synthesis of the apo-protein or from a posttranslational conversion of the Fe-S to the apo-protein form. This prompted a detailed analysis of how iron and NO regulate the RNA-binding activities of IRP and IRPB. We demonstrate that IRP is a relatively stable protein (half-life > 12 h). The induction of IRE-binding does not require de novo protein synthesis but results from conversion of Fe-S IRP to apo-IRP. In contrast, IRPB appears less stable in nonstarved cells (half-life approximately 4-6 h) and must be synthesized de novo following iron starvation. Our results furthermore reveal that two RNA-binding proteins with close structural and functional similarities that respond to the same cellular signals are regulated by predominantly different mechanisms.
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