Abstract
Nitric oxide (NO) produced from L-arginine by NO synthases (NOS) is a transmitter known to be involved in diverse biological processes, including immunomodulation, neurotransmission and blood vessel dilatation. We describe a novel role of NO as a signaling molecule in post-transcriptional gene regulation. We demonstrate that induction of NOS in macrophage and non-macrophage cell lines activates RNA binding by iron regulatory factor (IRFs), the central trans regulator of mRNAs involved in cellular iron metabolism. NO-induced binding of IRF to iron-responsive elements (IRE) specifically represses the translation of transfected IRE-containing indicator mRNAs as well as the biosynthesis of the cellular iron storage protein ferritin. These findings define a new biological function of NO and identify a regulatory connection between the NO/NOS pathway and cellular iron metabolism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Oxidoreductases / biosynthesis
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Amino Acid Oxidoreductases / metabolism*
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Animals
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Arginine / metabolism*
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Base Sequence
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Cell Line
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Chloramphenicol O-Acetyltransferase / metabolism
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Gene Expression Regulation, Enzymologic*
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Humans
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Iron / metabolism
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Iron-Regulatory Proteins
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Leukemia, Erythroblastic, Acute
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Macrophage Activation
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Macrophages / metabolism*
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Mice
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Models, Biological
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Molecular Sequence Data
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase
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Oligodeoxyribonucleotides
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Protein Biosynthesis
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RNA Probes
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RNA, Messenger / biosynthesis
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RNA, Messenger / metabolism*
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RNA-Binding Proteins / biosynthesis
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RNA-Binding Proteins / metabolism*
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Recombinant Fusion Proteins / metabolism
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Tumor Cells, Cultured
Substances
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Iron-Regulatory Proteins
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Oligodeoxyribonucleotides
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RNA Probes
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RNA, Messenger
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RNA-Binding Proteins
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Recombinant Fusion Proteins
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Nitric Oxide
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Arginine
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Iron
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Nitric Oxide Synthase
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Amino Acid Oxidoreductases
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Chloramphenicol O-Acetyltransferase