Department of Microbiology and Molecular Genetics, University of Texas Health Science Center-Houston and The University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030, USA.
Department of Microbiology and Physiological Systems, Albert Sherman Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
RNA. 2014 Jul;20(7):1057-67. doi: 10.1261/rna.043257.113. Epub 2014 May 23.
RNA degradation plays important roles for maintaining temporal control and fidelity of gene expression, as well as processing of transcripts. In Saccharomyces cerevisiae the RNA exosome is a major 3'-to-5' exoribonuclease and also has an endonuclease domain of unknown function. Here we report a physiological role for the exosome in response to a stimulus. We show that inactivating the exoribonuclease active site of Rrp44 up-regulates the iron uptake regulon. This up-regulation is caused by increased levels of reactive oxygen species (ROS) in the mutant. Elevated ROS also causes hypersensitivity to H2O2, which can be reduced by the addition of iron to H2O2 stressed cells. Finally, we show that the previously characterized slow growth phenotype of rrp44-exo(-) is largely ameliorated during fermentative growth. While the molecular functions of Rrp44 and the RNA exosome have been extensively characterized, our studies characterize how this molecular function affects the physiology of the organism.
RNA 降解在维持基因表达的时间控制和保真度以及转录本的加工方面起着重要作用。在酿酒酵母中,RNA 外切体是一种主要的 3'-5'外切核酸酶,也具有未知功能的内切核酸酶结构域。在这里,我们报告了外切体在响应刺激时的生理作用。我们表明,失活 Rrp44 的外切核酸酶活性位点会上调铁摄取调控基因。这种上调是由突变体中活性氧 (ROS) 水平的增加引起的。ROS 的增加还导致对 H2O2 的敏感性增加,而向 H2O2 应激细胞中添加铁可以降低 ROS 水平。最后,我们表明,rrp44-exo(-)的先前表征的生长缓慢表型在发酵生长过程中得到了很大改善。虽然 Rrp44 和 RNA 外切体的分子功能已得到广泛表征,但我们的研究描述了这种分子功能如何影响生物体的生理学。