The RNA exosome affects iron response and sensitivity to oxidative stress.
The RNA exosome affects iron response and sensitivity to oxidative stress.
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DOI：
10.1261/rna.043257.113
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
van Hoof A
中科院分区：
文献类型：
--
作者：
Tsanova B;Spatrick P;Jacobson A;van Hoof A
本文介绍了发现，灭活外泌体在酵母导致上调铁摄取调节子。上调是由活性氧水平增加引起的。这些观察结果表明，外泌体以某种方式影响生物体的生理学。RNA降解对于维持基因表达的时间控制和保真度以及转录物的加工起着重要作用。在酿酒酵母中，RNA外泌体是一种主要的3′至5′核糖核酸外切酶，也有一个功能未知的核酸内切酶结构域。在这里，我们报告了外泌体响应刺激的生理作用。我们发现，灭活核糖核酸外切酶活性位点的Rrp 44上调铁摄取调节子。这种上调是由突变体中活性氧（ROS）水平增加引起的。升高的ROS还引起对H2 O2的超敏反应，这可以通过向H2 O2应激的细胞中添加铁来降低。最后，我们表明，以前的特点是缓慢生长表型rrp 44-exo−在发酵生长过程中大大改善。虽然Rrp 44和RNA外泌体的分子功能已被广泛表征，但我们的研究表征了这种分子功能如何影响生物体的生理学。
This paper describes the finding that inactivating the exosome in yeast leads to up-regulation of the iron uptake regulon. The up-regulation is caused by increased levels of reactive oxygen species. These observations demonstrate that the exosome in some way affects the physiology of an organism. 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.
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