Aug 2026· PLoS ONE· Vol 21, pp. e0355681 - e0355681· 0 citations· 53 references
Medicine
TL;DR
Investigation of the regulatory mechanisms underlying nutrition-deprivation-responsive changes in gene expression in YGP1 revealed that the Puf5-mediated regulation contributes to the acid stress responses, and YGP1 expression supports cell survival in the puf5Δ background.
Abstract
Cells adapt to fluctuating nutrient conditions by dynamically regulating gene expression, ensuring survival under stress. Ygp1, a secretory yeast glycoprotein, is one such gene that is induced by nutrition deprivation, particularly glucose starvation. In this study, we investigated the regulatory mechanisms underlying nutrition-deprivation-responsive changes in gene expression, focusing on YGP1 expression. Under glucose-rich conditions, YGP1 expression was positively regulated by the RNA-binding protein Puf5, a member of the Puf family. This regulation ensured rhythmic YGP1 expression during M phase of the cell cycle. The Puf5-mediated control targeted a specific 60-nucleotide region in the YGP1 promoter (−600 to −540 from the start codon), and this regulation was partly mediated by the acid stress-responsive transcriptional activator Haa1. In addition, upon glucose exhaustion (diauxic shift), YGP1 expression was strongly induced by the stress-responsive transcription factors Msn2 and Msn4 through the stress-response elements in the YGP1 promoter. Further analysis of the physiological significance of YGP1 expression revealed that the Puf5-mediated regulation contributes to the acid stress responses, and YGP1 expression supports cell survival in the puf5Δ background. In summary, YGP1 expression is regulated by two distinct factors in a glucose availability-dependent manner: Puf5 under glucose-rich conditions and the Msn2/Msn4 during glucose starvation. Especially, Puf5-mediated regulation contributes to the acid stress responses and subsequently supports long-term cell survival.
Investigating how PKA regulates Msn2 subcellular localization and its impact on expression of PRC1, a representative vacuolar lumenal hydrolase, reveals that PKA-mediated regulation of Msn2 is essential for glucose stress responses and provides insight into how signaling pathways control PRC1 expression in yeast.
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