Multiple Post-Transcriptional Regulatory Mechanisms in Ferritin Gene Expression

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-03, Vol.86 (6), p.1801-1805
• Main Authors: Mattia, Elena, Den Blaauwen, Jan, Ashwell, Gilbert, Van Renswoude, Jos
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; Actins; AMINES; AMINO ACIDS; ANIMAL CELLS; ANIMALS; AUTORADIOGRAPHY; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOASSAY; Biological and medical sciences; BIOLOGICAL EFFECTS; BIOSYNTHESIS; CARBOXYLIC ACIDS; Cell culture techniques; Cell lines; Cell Nucleus - metabolism; CHELATING AGENTS; Complementary DNA; COMPLEXES; DAYS LIVING RADIOISOTOPES; DEFEROXAMINE; Deferoxamine - pharmacology; DIAGNOSTIC TECHNIQUES; DISEASES; DRUGS; EVEN-ODD NUCLEI; FERRITIN; Ferritins; Ferritins - biosynthesis; Ferritins - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genes. Genome; HEME; HEMIC DISEASES; Hemin - pharmacology; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; Humans; IMMUNE SYSTEM DISEASES; IMMUNOASSAY; IMMUNOLOGY; IN VITRO; Iron - pharmacology; IRON COMPLEXES; IRON COMPOUNDS; ISOTOPE APPLICATIONS; ISOTOPES; K562 cells; Kinetics; LEUKEMIA; Leukemia, Erythroblastic, Acute; LIGHT NUCLEI; LIPOTROPIC FACTORS; MAMMALS; MAN; MESSENGER-RNA; METALLOPROTEINS; METHIONINE; Molecular and cellular biology; Molecular genetics; NEOPLASMS; NUCLEI; Nucleic Acid Hybridization; NUCLEIC ACIDS; ODD-ODD NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; PIGMENTS; PORPHYRINS; PRIMATES; Protein Biosynthesis; PROTEINS; Protoporphyrins; RADIOASSAY; RADIOIMMUNOASSAY; RADIOIMMUNODETECTION; RADIOIMMUNOLOGY; RADIOISOTOPES; RNA; RNA, Messenger - biosynthesis; SULFUR 35; SULFUR ISOTOPES; SYNTHESIS; TRACER TECHNIQUES; TRANSCRIPTION; Transcription, Genetic; TRANSITION ELEMENT COMPLEXES; TRANSITION ELEMENT COMPOUNDS; TUMOR CELLS; Tumor Cells, Cultured; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.6.1801

We have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. We show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemininduced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. We conclude that iron-induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms. We propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H- and L-subunit mRNAs.