Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos (IATA), Consejo Superior de Investigaciones Científicas (CSIC), E-46980 Paterna, Valencia, Spain.
Department of Basic Medical Sciences, IRB-Lleida, University of Lleida, E-25198 Lleida, Spain.
Biochim Biophys Acta Gene Regul Mech. 2019 Sep;1862(9):194414. doi: 10.1016/j.bbagrm.2019.194414. Epub 2019 Aug 5.
Iron is an essential micronutrient that participates as a cofactor in a broad range of metabolic processes including mitochondrial respiration, DNA replication, protein translation and lipid biosynthesis. Adaptation to iron deficiency requires the global reorganization of cellular metabolism directed to optimize iron utilization. The budding yeast Saccharomyces cerevisiae has been widely used to characterize the responses of eukaryotic microorganisms to iron depletion. In this report, we used a genomic approach to investigate the contribution of transcription rates to the modulation of mRNA levels during adaptation of yeast cells to iron starvation. We reveal that a decrease in the activity of all RNA polymerases contributes to the down-regulation of many mRNAs, tRNAs and rRNAs. Opposite to the general expression pattern, many genes including components of the iron deficiency response, the mitochondrial retrograde pathway and the general stress response display a remarkable increase in both transcription rates and mRNA levels upon iron limitation, whereas genes encoding ribosomal proteins or implicated in ribosome biogenesis exhibit a pronounced fall. This expression profile is consistent with an activation of the environmental stress response. The phosphorylation stage of multiple regulatory factors strongly suggests that the conserved nutrient signaling pathway TORC1 is inhibited during the progress of iron deficiency. These results suggest an intricate crosstalk between iron metabolism and the TORC1 pathway that should be considered in many disorders.
铁是一种必需的微量元素，作为辅因子参与广泛的代谢过程，包括线粒体呼吸、DNA 复制、蛋白质翻译和脂质生物合成。对缺铁的适应需要细胞代谢的全局重组，以优化铁的利用。 budding yeast Saccharomyces cerevisiae 已被广泛用于描述真核微生物对缺铁的反应。在本报告中，我们使用基因组方法研究了转录速率对酵母细胞适应铁饥饿时 mRNA 水平调节的贡献。我们揭示了所有 RNA 聚合酶活性的降低有助于下调许多 mRNA、tRNA 和 rRNA。与一般表达模式相反，许多基因包括铁缺乏反应、线粒体逆行途径和一般应激反应的成分，在铁限制时转录速率和 mRNA 水平显著增加，而编码核糖体蛋白或参与核糖体生物发生的基因则明显下降。这种表达谱与环境应激反应的激活一致。多个调节因子的磷酸化阶段强烈表明，在缺铁过程中，保守的营养信号通路 TORC1 受到抑制。这些结果表明铁代谢和 TORC1 途径之间存在复杂的相互作用，在许多疾病中都应该考虑到这一点。
