Factors governing the transcriptome changes and chronological lifespan of fission yeast during phosphate starvation.

TitleFactors governing the transcriptome changes and chronological lifespan of fission yeast during phosphate starvation.
Publication TypeJournal Article
Year of Publication2024
AuthorsGarg A, Sanchez AM, Schwer B, Shuman S
JournalJ Biol Chem
Volume300
Issue3
Pagination105718
Date Published2024 Mar
ISSN1083-351X
KeywordsDNA-Binding Proteins, Gene Expression Regulation, Fungal, Longevity, Phosphates, RNA, Transfer, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Transcription Factors, Transcriptome
Abstract

Starvation of Schizosaccharomyces pombe for inorganic phosphate elicits adaptive transcriptome changes in which mRNAs driving ribosome biogenesis, tRNA biogenesis, and translation are globally downregulated, while those for autophagy and phosphate mobilization are upregulated. Here, we interrogated three components of the starvation response: upregulated autophagy; the role of transcription factor Pho7 (an activator of the PHO regulon); and upregulated expression of ecl3, one of three paralogous genes (ecl1, ecl2, and ecl3) collectively implicated in cell survival during other nutrient stresses. Ablation of autophagy factor Atg1 resulted in early demise of phosphate-starved fission yeast, as did ablation of Pho7. Transcriptome profiling of phosphate-starved pho7Δ cells highlighted Pho7 as an activator of genes involved in phosphate acquisition and mobilization, not limited to the original three-gene PHO regulon, and additional starvation-induced genes (including ecl3) not connected to phosphate dynamics. Pho7-dependent gene induction during phosphate starvation tracked with the presence of Pho7 DNA-binding elements in the gene promoter regions. Fewer ribosome protein genes were downregulated in phosphate-starved pho7Δ cells versus WT, which might contribute to their shortened lifespan. An ecl3Δ mutant elicited no gene expression changes in phosphate-replete cells and had no impact on survival during phosphate starvation. By contrast, pan-ecl deletion (ecl123Δ) curtailed lifespan during chronic phosphate starvation. Phosphate-starved ecl123Δ cells experienced a more widespread downregulation of mRNAs encoding aminoacyl tRNA synthetases vis-à-vis WT or pho7Δ cells. Collectively, these results enhance our understanding of fission yeast phosphate homeostasis and survival during nutrient deprivation.

DOI10.1016/j.jbc.2024.105718
Alternate JournalJ Biol Chem
PubMed ID38311173
PubMed Central IDPMC10910108
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 GM134021 / GM / NIGMS NIH HHS / United States
R35 GM126945 / GM / NIGMS NIH HHS / United States

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