Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonsense-mediated mRNA decay (NMD) prevents the accumulation of transcripts bearing premature termination codons. Here we show that Saccharomyces cerevisiae NMD mutants accumulate 5'-extended RNAs (CD-CUTs) of many subtelomeric genes. Using the subtelomeric ZRT1 and FIT3 genes activated in response to zinc and iron deficiency, respectively, we show that transcription of these CD-CUTs mediates repression at the bona fide promoters, by preventing premature binding of RNA polymerase II in conditions of metal repletion. Expression of the main ZRT1 CD-CUT is controlled by the histone deacetylase Rpd3p, showing that histone deacetylases can regulate expression of genes through modulation of the level of CD-CUTs. Analysis of binding of the transcriptional activator Zap1p and insertion of transcriptional terminators upstream from the Zap1p binding sites show that CD-CUT transcription or accumulation also interferes with binding of the transcriptional activator Zap1p. Consistent with this model, overexpressing Zap1p or using a constitutively active version of the Aft1p transcriptional activator rescues the induction defect of ZRT1 and FIT3 in NMD mutants. These results show that cryptic upstream sense transcription resulting in unstable transcripts degraded by NMD controls repression of a large number of genes located in subtelomeric regions, and in particular of many metal homeostasis genes.
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PMID:Cryptic transcription mediates repression of subtelomeric metal homeostasis genes. 2173 94

The Saccharomyces cerevisiae transcriptional activator Aft1 and its paralog Aft2 respond to iron deficiency by upregulating expression of proteins required for iron uptake at the plasma membrane, vacuolar iron transport, and mitochondrial iron metabolism, with the net result of mobilizing iron from extracellular sources and intracellular stores. Conversely, when iron levels are sufficient, Aft1 and Aft2 interact with the cytosolic glutaredoxins Grx3 and Grx4 and the BolA protein Bol2, which promote Aft1/2 dissociation from DNA and subsequent export from the nucleus. Previous studies unveiled the molecular mechanism for iron-dependent inhibition of Aft1/2 activity, demonstrating that the [2Fe-2S]-bridged Grx3-Bol2 heterodimer transfers a cluster to Aft2, driving Aft2 dimerization and dissociation from DNA. Here, we provide further insight into the regulation mechanism by investigating the roles of conserved cysteines in Aft2 in iron-sulfur cluster binding and interaction with [2Fe-2S]-Grx3-Bol2. Using size exclusion chromatography and circular dichroism spectroscopy, these studies reveal that both cysteines in the conserved Aft2 Cys-Asp-Cys motif are essential for Aft2 dimerization via [2Fe-2S] cluster binding, while only one cysteine is required for interaction with the [2Fe-2S]-Grx3-Bol2 complex. Taken together, these results provide novel insight into the molecular details of iron-sulfur cluster transfer from Grx3-Bol2 to Aft2 which likely occurs through a ligand exchange mechanism. Loss of either cysteine in the Aft2 iron-sulfur binding site may disrupt this ligand-exchange process leading to the isolation of a trapped Aft2-Grx3-Bol2 intermediate, while the replacement of both cysteines abrogates both the iron-sulfur cluster exchange and the protein-protein interactions between Aft2 and Grx3-Bol2.
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PMID:The conserved CDC motif in the yeast iron regulator Aft2 mediates iron-sulfur cluster exchange and protein-protein interactions with Grx3 and Bol2. 3149 53

Iron (Fe) is a major micronutrient which influences plant growth, development, quality and yield. Although basic helix-loop-helix (bHLH) transcription factors (TFs) which respond to iron deficiency have been identified, the molecular mechanisms have not been fully elucidated. In this study, a novel bHLH TF, NtbHLH1, was found to be induced by iron deficiency. Further analysis indicated that NtbHLH1 is localized to the nucleus and functions as a transcriptional activator. Moreover, overexpression of NtbHLH1 resulted in longer roots, altered rhizosphere pH and increased ferric-chelate reductase activity in iron deficient conditions. Overall these changes resulted in increased iron uptake relative to wild type plants. NtbHLH1 mutants, on the other hand, had an opposite phenotype. In addition, transcript levels of seven genes associated with iron deficiency response were higher in the NtbHLH1 overexpression transgenic plants and lower in ntbhlh1 relative to the WT under iron deficiency treatment. Taken together, these results demonstrated that NtbHLH1 plays a key role in iron deficiency response and they provide new insights into the molecular basis of iron homeostasis in tobacco.
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PMID:A novel bHLH transcription factor, NtbHLH1, modulates iron homeostasis in tobacco (Nicotiana tabacum L.). 3175 26