IRON-REGULATORY PROTEIN-1 (IRP-1) IS HIGHLY CONSERVED IN 2 INVERTEBRATE SPECIES - CHARACTERIZATION OF IRP-1 HOMOLOGS IN DROSOPHILA-MELANOGASTER AND CAENORHABDITIS-ELEGANS

Iron-regulatory protein-1 (IRP-1) plays a dual role as a regulatory RN A-binding protein and as a cytoplasmic aconitase. When bound to iron-r esponsive elements ORE), IRP-1 post-transcriptionally regulates the ex pression of mRNAs involved in iron metabolism. IRP have been cloned fr om several vertebrate species. Using a degenerate-primer PCR strategy and the screening of data bases, we now identify the homologues of IRP -1 in two invertebrate species, Drosophila melanogaster and Caenorhabd itis elegans. Comparative sequence analysis shows that these invertebr ate IRP are closely related to vertebrate IRP, and that the amino acid residues that have been implicated in aconitase function are particul arly highly conserved, suggesting that invertebrate IRP may function a s cytoplasmic aconitases. Antibodies raised against recombinant human IRP-1 immunoprecipitate the Drosophila homologue expressed from the cl oned cDNA. In contrast to vertebrates, two IRP-1 homologues (Drosophil a IRP-1A and Drosophila IRP-1B), displaying 86% identity to each other , are expressed in D. melanogaster: Both of these homologues are disti nct from vertebrate IRP-2. In contrast to the mammalian system where t he two IRP (IRP-1 and IRP-2) are differentially expressed, Drosophila IRP-1A and Drosophila IRP-1B are not preferentially expressed in speci fic organs. The localization of Drosophila IRP-1A to position 94C1-8 a nd of Drosophila IRP-1B to position 86B3-6 on the right arm of chromos ome 3 and the availability of an IRP-1 cDNA from C. elegans will facil itate a genetic analysis of the IRE/IRP system, thus opening a new ave nue to explore this regulatory network.