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. 1993 Sep;12(9):3651–3657. doi: 10.1002/j.1460-2075.1993.tb06039.x

Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway.

G Weiss 1, B Goossen 1, W Doppler 1, D Fuchs 1, K Pantopoulos 1, G Werner-Felmayer 1, H Wachter 1, M W Hentze 1
PMCID: PMC413641  PMID: 7504627

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.

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