Mechanism of gene activation by iron

铁(Fe)是大多数生物体的关键营养物质。这种金属普遍存在于铁利用酶的活性部位，这些酶参与代谢途径，如三羧酸(TCA)循环、呼吸、氧运输、DNA合成和代谢物的合成。虽然铁是地球上最丰富的金属之一，但由于在中性pH值的好氧条件下溶解性差，几乎无法接触到铁。在缺铁条件下的生长过程中，细菌会在其环境中分泌一种称为铁载体的低分子分子(称为肠动素或肠球蛋白)，在铁通过铁获取蛋白运输到细胞内之前，这种分子会使铁溶解。因此，当细胞内铁水平较高时，蛋白质Fur(铁摄取调节因子)抑制铁摄取基因的转录启动，铁是辅助因子。与此相反，我们已经证明了几个基因的转录在细胞内高铁的条件下被激活，或者在特定的小RNA存在的情况下被激活。这些基因总共15个，分成10个操纵子。它们中的几个直接参与铁代谢(例如铁蛋白)，而其他的功能未知。这种铁依赖的转录激活机制尚不清楚。我们的研究项目解决了这些基因的激活机制以及它们的功能。

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.