CHARACTERIZATION AND EXPRESSION OF IRON REGULATORY PROTEIN-2 (IRP2) - PRESENCE OF MULTIPLE IRP2, TRANSCRIPTS REGULATED BY INTRACELLULAR IRON LEVELS

Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to stem-loop structures, termed iron-responsive elements (IREs), present in either the 5'- or 3'-untranslated regions of specific mRNAs. The binding of IRPs to 5'-IREs inhibits translation of mRNA, whereas the binding of IRPs to 3'-IREs stabilizes mRNA. To study the structure and regulation of IRP2, we isolated cDNAs for rat and human IRP2. The derived amino acid sequence of rat IPR2 is 93% identical with that of human IRP2 and is present in lower eukaryotes, indicating that IRP2 is highly conserved, IRP1 and IRP2 share 61% overall amino acid identity, IRP2 is ubiquitously expressed in rat tissues, the highest amounts present in skeletal muscle and heart, IRP2 is encoded by multiple mRNAs of 6.4, 4.0, and 3.7 kilobases, The 3'-untranslated region of rat IRP2 contains multiple polyadenylation signals, two of which could account for the 4.0 kb and 3.7-kb mRNAs, The 3.7-kb mRNA is increased in iron-depleted cells and occurs with a reciprocal decrease in the 6.4-kb transcript, These data suggest that the 3.7-kb mRNA is produced by alternative poly(A) site utilization in iron-depleted cells.