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Regulating iron storage and metabolism with RNA: an overview of posttranscriptional controls of intracellular iron homeostasis

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Abstract Iron (Fe) is a double‐edged sword for most living organisms. Although it is essential for the catalytic activity of a large number of enzymes, ferrous iron (Fe2+) becomes cytotoxic in the presence of normal respiratory by‐products such as H2O2. Because of this toxicity, intracellular iron concentrations ought to be regulated by elaborated homeostasis systems that, despite decades of extensive studies, have not yet revealed all of their surprising arrays of mechanistic details. Within the last few years, our understanding of iron metabolism has revealed that posttranscriptional regulation represents a major contribution to iron homeostasis in a host of organisms. While the small RNA RyhB regulates iron homeostasis in bacteria, its functional homolog protein Cth2 performs a similar task in yeasts. Recent advances in the elucidation of the mechanism of action and functions of RyhB have been made in Escherichia coli. In addition, other RyhB‐like small RNAs have been identified in several bacterial species, such as Pseudomonas aeruginosa, Salmonella enterica, Vibrio cholerae, Neisseria meningitidis, and Shigella spp. These recent findings have shed light on the complexity of iron homeostasis. WIREs RNA 2012, 3:26–36. doi: 10.1002/wrna.102 This article is categorized under: Translation > Translation Regulation RNA Turnover and Surveillance > Regulation of RNA Stability Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease

RyhB as a master regulator of Fe homeostasis. (A) Under conditions of Fe abundance, Fur binds Fe2+ and represses the transcription initiation of ryhB. (B) When Fe becomes scarce, Fur becomes inactive and RyhB is rapidly expressed. RyhB then promotes a metabolic remodeling in response to Fe starvation by (1) stimulating the degradation of at least 18 mRNAs encoding Fe‐using proteins, by (2) repressing the translation of fur mRNA through base pairing with the uof region, and by (3) promoting the degradation of iscSUA transcripts, resulting in the accumulation of stable iscR transcript. RyhB also promotes siderophore production by (4) repressing the translation of cysE mRNA, which allows more serine to be used for enterobactin production to the detriment of cysteine biosynthesis, and by (5) activating shiA mRNA translation to increase shikimate acquisition from the environment.

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Translation > Translation Regulation
RNA Turnover and Surveillance > Regulation of RNA Stability
Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs
RNA in Disease and Development > RNA in Disease

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