Evaluation of the iron regulatory protein-1 interactome.

The interactions of iron regulatory proteins (IRPs) with mRNAs containing an iron-responsive element (IRE) is a major means through which intracellular iron homeostasis is maintained and integrated with cellular function. Although IRE-IRP interactions have been proposed to modulate the expression of a diverse number of mRNAs, a transcriptome analysis of the interactions that form within the native mRNA structure and cellular environment has not previously been described. An RNA-CLIP study is described here that identified IRP-1 interactions occurring within a primary cell line expressing physiologically relevant amounts of mRNA and protein. The study suggests that only a small subset of the previously proposed IREs interact with IRP-1 in situ. Identifying authentic IRP interactions is not only important to a greater understanding of iron homeostasis and its integration with cell biology but also to the development of novel therapeutics that can compensate for iron imbalances.