Mechanism of gene activation by iron

铁激活基因的机制

• 批准号: 326831-2006
• 负责人: Masse, Eric
• 金额: $ 3.34万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=337431
• 关键词: Mechanism; gene; activation; iron

Iron (Fe) is a key nutrient for most organisms. This metal is universally present in the active site of iron-utilizing enzymes, which are involved in metabolic pathways such as the tricarboxylic acid (TCA) cycle, respiration, oxygen transport, DNA synthesis, and synthesis of metabolites. Although iron is one of the most abundant metals on earth, it is nearly inaccessible because of poor solubility in aerobic conditions at neutral pH. During growth under iron depletion conditions, bacteria secrete in their environment low-molecular weight molecules called siderophores (named enterobactin or enterochelin), which makes the iron soluble before it is transported inside the cell through iron acquisition proteins. Thus, when intracellular iron level is high, the protein Fur (Ferric uptake regulator) represses transcription initiation of iron uptake genes, with iron as a co-factor. In contrast with this, we have shown that transcription of several genes is activated under conditions of high intracellular iron, or in the presence of a specific small RNA. These genes, 15 in total, are grouped in 10 operons. Several of them are directly involved in iron metabolism (e.g. ferritin) while other have unknown function. This mechanism of iron-dependent transcriptional activation remains unclear. Our research program addresses the mechanism of activation of these genes as well as their functions.

铁 (Fe) 是大多数生物体的关键营养素。这种金属普遍存在于铁利用酶的活性位点，这些酶参与三羧酸（TCA）循环、呼吸、氧运输、DNA 合成和代谢物合成等代谢途径。尽管铁是地球上最丰富的金属之一，但由于在中性 pH 值的有氧条件下溶解度差，因此几乎无法获取。在缺铁条件下生长期间，细菌在其环境中分泌称为铁载体（称为肠杆菌素或肠螯素）的低分子量分子，这使得铁在通过铁获取蛋白转运到细胞内之前可溶。因此，当细胞内铁水平较高时，蛋白质 Fur（铁摄取调节剂）会抑制铁摄取基因的转录起始，而铁作为辅助因子。与此相反，我们发现一些基因的转录在细胞内铁含量高或存在特定小RNA的条件下被激活。这些基因总共 15 个，分为 10 个操纵子。其中一些直接参与铁代谢（例如铁蛋白），而另一些则具有未知的功能。这种铁依赖性转录激活的机制仍不清楚。我们的研究计划致力于研究这些基因的激活机制及其功能。