Research Article: Pop2 phosphorylation at S39 contributes to the glucose repression of stress response genes, HSP12 and HSP26

Date Published: April 11, 2019

Publisher: Public Library of Science

Author(s): Pham Thi Kim Lien, Nguyen Thi Minh Viet, Tomoaki Mizuno, Yasuyuki Suda, Kenji Irie, Reiko Sugiura.

http://doi.org/10.1371/journal.pone.0215064

Abstract

The S. cerevisiae Pop2 protein is an exonuclease in the Ccr4-Not complex that is a conserved regulator of gene expression. Pop2 regulates gene expression post-transcriptionally by shortening the poly(A) tail of mRNA. A previous study has shown that Pop2 is phosphorylated at threonine 97 (T97) by Yak1 protein kinase in response to glucose limitation. However, the physiological importance of Pop2 phosphorylation remains unknown. In this study, we found that Pop2 is phosphorylated at serine 39 (S39) under unstressed conditions. The dephosphorylation of S39 was occurred rapidly after glucose depletion, and the addition of glucose to the glucose-deprived culture recovered this phosphorylation, suggesting that Pop2 phosphorylation at S39 is regulated by glucose. This glucose-regulated phosphorylation of Pop2 at S39 is dependent on Pho85 kinase. We previously reported that Pop2 takes a part in the cell wall integrity pathway by regulating LRG1 mRNA; however, S39 phosphorylation of Pop2 is not involved in LRG1 expression. On the other hand, Pop2 phosphorylation at S39 is involved in the expression of HSP12 and HSP26, which encode a small heat shock protein. In the medium supplemented with glucose, Pop2 might be phosphorylated at S39 by Pho85 kinase, and this phosphorylation contributes to repress the expression of HSP12 and HSP26. Glucose starvation inactivated Pho85, which resulted in the derepression of HSP12 and HSP26, together with other glucose sensing mechanisms. Our results suggest that Pho85-dependent phosphorylation of Pop2 is a part of the glucose sensing system in yeast.

Partial Text

Post-transcriptional regulation, including the control of mRNA degradation and translation, plays important roles in regulation of gene expression. mRNA degradation is generally initiated by poly(A) tail shortening referred to as deadenylation, which is catalyzed by the Ccr4-Not and the Pan2-Pan3 complexes [1]. In Saccharomyces cerevisiae, the Ccr4-Not complex consists of 9 core subunits, including Ccr4, Pop2/Caf1, Caf40, Caf130 and Not1-5, all of which have homologs in most other eukaryotes [2]. Ccr4 and Pop2 are two active 3’ to 5’ exonucleases: Ccr4 is the major one; Pop2 may modulate specific mRNA expression in certain conditions [1]. Pop2 is reportedly involved in expression control of glucose-repressed genes and regulation of the cell wall integrity (CWI) pathway in S. cerevisiae [3, 4]. The loss of POP2 results in pleiotropic phenotypes including temperature-sensitive growth, abnormal cell morphology, weak cell lysis and defective glucose repression [3, 5]. Pop2 is phosphorylated by Yak1 kinase at threonine 97 (T97) in response to a glucose-regulating signal [6]. This modification is required for cell growth control and cell cycle arrest at G1 phase after glucose starvation [6]. We have previously shown that Pop2 functions in the CWI pathway by regulating the expression of LRG1, encoding a GTPase-activating protein for Rho1 small GTPase [4]. The LRG1 mRNA level is elevated in pop2Δ and the high temperature-sensitivity phenotype caused by pop2Δ mutation is suppressed by deletion of LRG1 [4].

Taken together, we have shown that Pop2 is phosphorylated in a Pho85-dependent manner and this phosphorylation contributes to glucose repression of stress response genes, HSP12 and HSP26. Based on the present data, Fig 8 shows our proposed model. Our study provides valuable insights the role of Pop2 in glucose repression of stress responses in yeast. The molecular mechanism how Pop2 regulates HSP12 and HSP26 mRNAs through S39 phosphorylation will be the focus of future studies.

 

Source:

http://doi.org/10.1371/journal.pone.0215064

 

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