A ferroportin transcript that lacks an iron-responsive element enables duodenal and erythroid precursor cells to evade translational repression.
Ferroportin (FPN1), the sole characterized mammalian iron exporter, has an iron-responsive element (IRE) in its 5' untranslated region, which ensures that its translation is repressed by iron regulatory proteins (IRPs) in iron-deficient conditions to maintain cellular iron content. However, here we demonstrate that duodenal epithelial and erythroid precursor cells utilize an alternative upstream promoter to express a FPN1 transcript, FPN1B, which lacks the IRE and is not repressed in iron-deficient conditions. The FPN1B transcript encodes ferroportin with an identical open reading frame and contributes significantly to ferroportin protein expression in erythroid precursors and likely also in the duodenum of iron-starved animals. The identification of FPN1B reveals how FPN1 expression can bypass IRP-dependent repression in intestinal iron uptake, even when cells throughout the body are iron deficient. In erythroid precursor cells, we hypothesize that FPN1B expression enhances real-time sensing of systemic iron status and facilitates restriction of erythropoiesis in response to low systemic iron.
Molecular Medicine Program, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
De-Liang
DL
Zhang
Robert M
RM
Hughes
Hayden
H
Ollivierre-Wilson
Manik C
MC
Ghosh
Tracey A
TA
Rouault
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004386:Duodenum / Q000201:enzymology / Q000378:metabolism*; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D035925:Iron-Regulatory Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D020218:Response Elements; D016415:Sequence Alignment; D014158:Transcription, Genetic; D000098742:Ferroportin
D020121:5' Untranslated Regions; D027682:Cation Transport Proteins; D035925:Iron-Regulatory Proteins; D000098742:Ferroportin; D007501:Iron