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The RNA Exosome Affects Iron Response And Sensitivity To Oxidative Stress

Borislava Tsanova, Phyllis Spatrick, Allan Jacobson, Ambro van Hoof

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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.