Iron-regulatory protein-1 (IRP-1) is highly conserved in two invertebrate species - Characterization of IRP-1 homologues in Drosophila melanogaster and Caenorhabditis elegans

Martina Muckenthaler, Niki Gunkel, Dmitrij Frishman, Anna Cyrklaff, Pavel Tomancak, Matthias W. Hentze

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Iron-regulatory protein-1 (IRP-1) plays a dual role as a regulatory RNA- binding protein and as a cytoplasmic aconitase. When bound to iron-responsive elements (IRE), IRP-1 post-transcriptionally regulates the expression of mRNAs involved in iron metabolism. IRP have been cloned from 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 Caenorhabditis elegans. Comparative sequence analysis shows that these invertebrate IRP are closely related to vertebrate IRP, and that the amino acid residues that have been implicated in aconitase function are particularly highly conserved, suggesting that invertebrate IRP may function as cytoplasmic aconitases. Antibodies raised against recombinant human IRP-1 immunoprecipitate the Drosophila homologue expressed from the cloned cDNA. In contrast to vertebrates, two IRP-1 homologues (Drosophila IRP-1A and Drosophila IRP-1B), displaying 86% identity to each other, are expressed in D. melanogaster. Both of these homologues are distinct from vertebrate IRP-2. In contrast to the mammalian system where the two IRP (IRP-1 and IRP-2) are differentially expressed, Drosophila IRP-1A and Drosophila IRP-1B are not preferentially expressed in specific organs. The localization of Drosophila IRP-1A to position 94C1-8 and of Drosophila IRP- 1B to position 86B3-6 on the right arm of chromosome 3 and the availability of an IRP-1 cDNA from C. elegans will facilitate a genetic analysis of the IRE/IRP system, thus opening a new avenue to explore this regulatory network.

Original languageEnglish
Pages (from-to)230-237
Number of pages8
JournalEuropean Journal of Biochemistry
Volume254
Issue number2
DOIs
StatePublished - 1 Jun 1998
Externally publishedYes

Keywords

  • Caenorhabditis elegans
  • Drosophila melanogaster
  • Iron regulation
  • Iron-regulatory protein
  • RNA binding

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