Superfund Research Program
Comparative and Functional Genomics Analysis of Superfund Toxicants
Project Leader: Paul Russell (The Scripps Research Institute)
Grant Number: P42ES010337
Funding Period: 2000-2017
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Dr. Russell’s project is focused on using genetic and post-genome technologies to better understand how microorganisms survive exposure to environmental pollutants that cause oxidative stress. The team’s goal is to make fundamental discoveries that will be broadly applicable to human health and bioremediation. These experiments are being carried out with the fission yeast Schizosaccharomyces pombe, a model organism that has been used to pioneer numerous discoveries in many areas of cell biology. The highlight of the researchers’ previous update was the discovery of Csx1. Their studies showed that Csx1 exerts global control over gene expression in response to oxidative stress. It does so by binding to specific mRNA species and stabilizing them. One of its major targets is atf1 mRNA. Atf1 is a transcription factor subunit that is homologous to the human AP-1 related transcription factors. Having established that Csx1 plays a crucial role in regulating gene expression in response to oxidative stress, the researchers then undertook experiments to better understand how Csx1 stabilizes mRNAs during oxidative stress. Their approach was to identify proteins that associate with Csx1 in a physiologically significant manner. They used Multidimensional Protein Identification Technology (MudPIT), a highly sensitive method of protein identification that uses nanoscale strong cation exchange liquid chromatography upstream of reversed phase liquid chromatography online with microelectrospray mass spectrometry. By these methods the research team identified two novel proteins, Cip1 and Cip2. These proteins are related to each other and contain RNA Recognition Motifs (RRMs). A combination of genetic and biochemical studies strongly indicate that Csx1 and Csx2 are involved in degrading mRNAs that are protected by Csx1.