Fig. 4

Iron transporter isoforms. a Alternate transcripts for DMT1. Exons are represented by blocks, introns by lines. Blocks are solid when the exons are found in mature mRNA but open when not (and instead untranscribed or part of an intron) except that 16A is stippled to emphasize when it is retained as part of an extended exon. Selection of one of the two promoters—1A [23] or 1B—leads to a choice of 5′ ends for DMT1 mRNA. Exons 2–15 are processed next (there is some alternate splicing for these but the physiological role is not yet defined). If polyadenylation occurs at the end of exon 16/16A, the entire exon remains in mature mRNA. The exon includes an iron-responsive element (IRE) that potentially can be bound by an iron regulatory protein (IRP). The mRNA will thus contain an IRE in the 3′ untranslated region (UTR). If polyadenylation occurs instead at the end of the next exon (17), splicing occurs from a small part of the preceding exon (16) and the IRE, and the remainder of 16A is part of the intron. This set of choices was first noted for rats [10], but soon also for humans [29]. Although the mRNA variants (1A, 1B, +IRE, −IRE) are frequently labeled alternative splicing, they actually represent alternate promoters and poly A sites. b The protein isoforms of DMT1. Human DMT1 has 543 internal amino acid residues common to all 4 forms here represented by black lines. Exon 1A contains an AUG codon, so it has 29 amino acid residues at the N-terminus (here represented by a dark gray line) encoded by exons 1A and 2. Exon 1B lacks an AUG, so the first amino acid residue (next AUG) is encoded within exon 2. Exon 17 encodes 25 unique amino acid residues, most conveniently designated −IRE and here represented by a light gray line. Exon 16A encodes 18 unique amino acid residues, most conveniently designated +IRE and here represented by a gray line. c Alternate transcripts for Fpn. As in a, exons are represented by blocks, introns by lines. Blocks are solid when the exons are found in mature mRNA but open when not (and instead untranscribed or part of an intron) except that parts of 1a are stippled to suggest how frequently they are retained as part of the exon when the 1b promoter initiates transcription. Selection of one of the two promoters—1a or b [57]—leads to a choice of 5′ ends for Fpn mRNA. (It is unfortunate that the authors chose to designate 1a and b in a fashion inconsistent with the choices made years earlier for DMT1 but this is their nomenclature.) When the 1b promoter is used, splicing proceeds from the 3′ donor sequence of exon 1b to one of the 3 possible splice acceptors within what is wholly exon 1a if the 1a promoter was to be selected. All 3 acceptors are 3′ to the IRE so any of the 3 transcripts that start from exon 1b exclude the IRE. This figure is based on data from Rouault’s group [57], but not modified from their figures