title: Expression of alternative transcripts of ferroportin-1 during human erythroid differentiation.
abstract: OBJECTIVE
  Ferroportin-1 (FPN1) is expressed in various types of cells that play critical roles in mammalian iron metabolism and appears to act as an iron exporter in these tissues. The aim of this study was to investigate whether erythroid cells possess specific mechanisms for iron export.
  
  
  METHODS
  The expression of FPN1 during human erythroid differentiation, the characterization of alternative transcripts, the modulation by iron and the subcellular localization of this protein were studied.
  
  
  RESULTS
  FPN1 mRNA and protein are highly expressed during human erythroid differentiation. The iron-responsive element (IRE) in the 5'- untranslated region (UTR) of FPN1 mRNA is functional but, in spite of that, FPN1 protein expression, as well as mRNA level and half-life, seem not to be affected by iron. To explain these apparenthy discordant results we searched for alternative transcripts of FPN1 and found at least three different types of transcripts, displaying alternative 5' ends. Most of the FPN1 transcripts code for the canonical protein, but only half of them contain an IRE in the 5'-UTR and have the potential to be translationally regulated by iron. Expression analysis shows that alternative FPN1 transcripts are differentially expressed during erythroid differentiation. Finally, sustained expression of alternative FPN1 transcripts is apparently observed only in erythroid cells.
  
  
  CONCLUSIONS
  This is the first report describing the presence of FPN1 in erythroid cells at all stages of differentiation, providing evidence that erythroid cells possess specific mechanisms of iron export. The existence of multiple FPN1 transcripts indicates a complex regulation of the FPN1 gene in erythroid cells.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cianetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Segnalini
authors.forename: Alessia
authors.initials: A
authors.lastname: Calzolari
authors.forename: Ornella
authors.initials: O
authors.lastname: Morsilli
authors.forename: Federica
authors.initials: F
authors.lastname: Felicetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Ramoni
authors.forename: Marco
authors.initials: M
authors.lastname: Gabbianelli
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
authors.forename: Nadia Maria
authors.initials: NM
authors.lastname: Sposi
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006207:Half-Life; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000494:pharmacology; D020014:K562 Cells / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009928:Organ Specificity; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000737:chemistry / Q000648:ultrastructure; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D020121:5' Untranslated Regions; D027682:Cation Transport Proteins; D007502:Iron Chelating Agents; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000098742:Ferroportin; D007501:Iron; D003676:Deferoxamine