期刊
EUKARYOTIC CELL
卷 9, 期 3, 页码 460-471出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/EC.00213-09
关键词
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资金
- Deutsche Forschungsgemeinschaft [SFB 593, GRK 1216]
- von Behring-Rontgen Stiftung
- Max-Planck Gesellschaft
- Fonds der chemischen Industrie
Budding yeast (Saccharomyces cerevisiae) responds to iron deprivation both by Aft1-Aft2-dependent transcriptional activation of genes involved in cellular iron uptake and by Cth1-Cth2-specific degradation of certain mRNAs coding for iron-dependent biosynthetic components. Here, we provide evidence for a novel principle of iron-responsive gene expression. This regulatory mechanism is based on the modulation of transcription through the iron-dependent variation of levels of regulatory metabolites. As an example, the LEU1 gene of branched-chain amino acid biosynthesis is downregulated under iron-limiting conditions through depletion of the metabolic intermediate alpha-isopropylmalate, which functions as a key transcriptional coactivator of the Leu3 transcription factor. Synthesis of alpha-isopropylmalate involves the iron-sulfur protein Ilv3, which is inactivated under iron deficiency. As another example, decreased mRNA levels of the cytochrome c-encoding CYC1 gene under iron-limiting conditions involve heme-dependent transcriptional regulation via the Hap1 transcription factor. Synthesis of the iron-containing heme is directly correlated with iron availability. Thus, the iron-responsive expression of genes that are downregulated under iron-limiting conditions is conferred by two independent regulatory mechanisms: transcriptional regulation through iron-responsive metabolites and post-transcriptional mRNA degradation. Only the combination of the two processes provides a quantitative description of the response to iron deprivation in yeast.
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