Stabilizing RNA in Response to Stress

Abstract

In a protective response to oxidative stress, mammalian cells trigger a rapid mitogen-activated protein kinase (MAPK)-signaling cascade that controls specific transcription factors and the expression of genes necessary for survival. The fission yeast Schizosaccharomyces pombe uses a similar stress-activated response pathway that includes a MAPK called Spc1 and a transcription factor called Atf1 that controls the expression of over 200 genes in response to oxidative stress. Spc1 phosphorylates Aft1, but a mechanism of control has not been clear. Rodriguez-Gabriel et al. report that the Spc1 response pathway requires a protein called Csx1 to bind to and stabilize mRNA encoding Atf1. Yeast lacking functional Csx1 were insensitive to oxidative stress, although Spc1 was still activated. These mutant yeast also did not display an increase in atf1 mRNA observed in wild-type cells and also had a reduced number of genes expressed in response to oxidative stress. Csx1 contains RNA recognition motifs that are typically found in regulators of RNA processing. In response to oxidative stress, Csx1 became phosphorylated and associated with aft1 mRNA. In the absence of Csx1, aft1 mRNA had a reduced half-life, indicating that the interaction is required for mRNA stability. The authors propose that Csx1 and Spc1 control atf1 mRNA turnover under oxidative stress conditions. Stabilizing preexisting mRNA in the cytoplasm may ensure rapid protein synthesis required for cellular protection under such conditions. M.A. Rodriguez-Gabriel, G. Burns, W. H. McDonald, V. Martin, J. R. Yates III, J. Bahler, P. Russell, RNA-binding protein Csx1 mediates global control of gene expression in response to oxidative stress. EMBO J. 22 , 6256-6266 (2003). [Abstract] [Full Text]