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InsP₇ phosphatase Siw14 regulates inositol pyrophosphate levels to control localization of the general stress response transcription factor Msn2

Steidle, Elizabeth A. and Morrissette, Victoria A. and Fujimaki, Kotaro and Chong, Lucy and Resnick, Adam C. and Capaldi, Andrew P. and Rolfes, Ronda J. (2020) InsP₇ phosphatase Siw14 regulates inositol pyrophosphate levels to control localization of the general stress response transcription factor Msn2. Journal of Biological Chemistry, 295 (7). pp. 2043-2056. ISSN 0021-9258.

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The environmental stress response (ESR) is critical for cell survival. Yeast cells unable to synthesize inositol pyrophosphates (PP-InsPs) are unable to induce the ESR. We recently discovered a diphosphoinositol pentakisphosphate (PP-InsP5) phosphatase in Saccharomyces cerevisiae encoded by SIW14. Yeast strains deleted for SIW14 have increased levels of PP-InsPs. We hypothesized that strains with high inositol pyrophosphate levels will have an increased stress response. We examined the response of the siw14Δ mutant to heat shock, nutrient limitation, osmotic stress, and oxidative treatment using cell growth assays and found increased resistance to each. Transcriptional responses to oxidative and osmotic stresses were assessed using microarray and reverse transcriptase quantitative PCR. The ESR was partially induced in the siw14Δ mutant strain, consistent with the increased stress resistance, and the mutant strain further induced the ESR in response to oxidative and osmotic stresses. The levels of PP-InsPs increased in WT cells under oxidative stress but not under hyperosmotic stress, and they were high and unchanging in the mutant. Phosphatase activity of Siw14 was inhibited by oxidation that was reversible. To determine how altered PP-InsP levels affect the ESR, we performed epistasis experiments with mutations in rpd3 and msn2/4 combined with siw14Δ. We show that mutations in msn2Δ and msn4Δ, but not rpd3, are epistatic to siw14Δ by assessing growth under oxidative stress conditions and expression of CTT1. Msn2-GFP nuclear localization was increased in the siw14Δ. These data support a model in which the modulation of PP-InsPs influence the ESR through general stress response transcription factors Msn2/4.

Item Type:Article
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URLURL TypeDescription Information
Chong, Lucy0000-0002-5858-9984
Additional Information:© 2020 Steidle et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, December 3, 2019 Published, Papers in Press, December 17, 2019. We thank Tanaporn Wangsanut for help with RNA extractions, Erica Raphael for help with strain construction, and Chamel Khoury for initial observations that started this project. We thank Audrey Gasch and Mark Rose for providing yeast strains, Jingwen Hu and Jeff Huang for providing catalase, and Mark Rose for use of the fluorescent microscope and for advice. This work was supported by a Georgetown Pilot Grant (to R. J. R.), a GradGov Research Project Award (to V. A. M.), National Institutes of Health Grant R01GM097329 (to A. P. C.), and National Science Foundation CAREER Grant MCB-1253809 (to A. C. R.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The microarray data reported in this paper have been submitted to the Gene Expression Omnibus (GEO) database under GEO accession no. GSE135546.
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Georgetown UniversityUNSPECIFIED
Subject Keywords:Saccharomyces cerevisiae; stress response; transcription regulation; gene expression; yeast genetics; inositol pyrophosphate; MSN2; SIW14
Issue or Number:7
Record Number:CaltechAUTHORS:20200319-103342094
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Official Citation:Elizabeth A. Steidle, Victoria A. Morrissette, Kotaro Fujimaki, Lucy Chong, Adam C. Resnick, Andrew P. Capaldi, and Ronda J. Rolfes. The InsP7 phosphatase Siw14 regulates inositol pyrophosphate levels to control localization of the general stress response transcription factor Msn2. J. Biol. Chem. 2020 295: 2043-2056. doi:10.1074/jbc.RA119.012148
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101995
Deposited By: Tony Diaz
Deposited On:19 Mar 2020 17:55
Last Modified:19 Mar 2020 17:55

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