Glucose-Regulated Phosphorylation of the PUF Protein Puf3 Regulates the Translational Fate of Its Bound mRNAs and Association with RNA Granules

Lee, Chien Der; Tu, Benjamin P.

doi:10.1016/j.celrep.2015.05.014

Cited by 90 publications

(118 citation statements)

References 55 publications

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“…Recently, Puf3p was shown to become phosphorylated at this and other residues when cells are deprived of glucose. This phosphorylation promotes the translation of bound transcripts that encode mitochondrial proteins (45). In line with this finding, our quantitative proteome analysis revealed reduced abundances of plenty of mitochondrial proteins, including ribosomal proteins and subunits of the transporter complexes of the outer and inner mitochondrial membranes, in the asc1 Ϫ strain (see Table S8 in the supplemental material).…”

Section: Discussionsupporting

confidence: 80%

Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling

Schmitt

Smolinski

Neumann

et al. 2017

Molecular and Cellular Biology

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WD40 repeat proteins fold into characteristic ␤-propeller structures and control signaling circuits during cellular adaptation processes within eukaryotes. The RACK1 protein of Saccharomyces cerevisiae, Asc1p, consists exclusively of a single sevenbladed ␤-propeller that operates from the ribosomal base at the head region of the 40S subunit. Here we show that the R38D K40E ribosomal binding-compromised variant (Asc1DEp) is severely destabilized through mutation of phosphosite T143 to a dephosphorylation-mimicking alanine, probably through proteasomal degradation, leading to asc1 Ϫ phenotypes. Phosphosite Y250 contributes to resistance to translational inhibitors but does not influence Asc1DEp stability. Beyond its own phosphorylation at T143, Y250, and other sites, Asc1p heavily influences the phosphorylation of as many as 90 proteins at 120 sites. Many of these proteins are regulators of fundamental processes ranging from mRNA translation to protein transport and turnover, cytoskeleton organization, and cellular signaling. Our data expose Asc1p/ RACK1 as a key factor in phosphosignaling and manifest it as a control point at the head of the ribosomal 40S subunit itself regulated through posttranslational modification.

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Section: Discussionsupporting

confidence: 80%

Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling

Schmitt

Smolinski

Neumann

et al. 2017

Molecular and Cellular Biology

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“…Examples are Mlo3 [75], the polyA-binding protein Nab2 [76] and Mcp2, an ortholog of budding yeast Puf3 that regulates the translation and stability of mRNAs encoding mitochondrial proteins [77]. These results indicate that post-transcriptional levels of regulation play important roles in the control of energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Functional and regulatory profiling of energy metabolism in fission yeast

et al. 2016

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BackgroundThe control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration.ResultsWe screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. Growth media and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene-expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in energy metabolism pathways are coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that acetyl-CoA synthase, rather than citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction.ConclusionsThis study provides a rich framework of the genetic and regulatory basis of energy metabolism in fission yeast and beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for investigating metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1101-2) contains supplementary material, which is available to authorized users.

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“…mRNAs bearing a Puf3‐binding motif are associated with translational downregulation following exposure to hydrogen peroxide, while the protein's polysome association also reduces under these conditions (Rowe et al, ). Puf3 becomes phosphorylated in its N ‐terminal unstructured region during glucose starvation, which switches the fate of its target mRNAs by promoting their enhanced translation (Lee & Tu, ). This is consistent with Puf3 contributing to the cellular response to stress by promoting the expression of mitochondrially destined proteins for enhanced respiratory growth.…”

Section: Mrna‐specific Regulation: Roles Of Mrna‐binding Proteinsmentioning

confidence: 99%

Translational regulation in response to stress in Saccharomyces cerevisiae

Crawford

Pavitt

2018

Yeast

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The budding yeast Saccharomyces cerevisiae must dynamically alter the composition of its proteome in order to respond to diverse stresses. The reprogramming of gene expression during stress typically involves initial global repression of protein synthesis, accompanied by the activation of stress-responsive mRNAs through both translational and transcriptional responses. The ability of specific mRNAs to counter the global translational repression is therefore crucial to the overall response to stress. Here we summarize the major repressive mechanisms and discuss mechanisms of translational activation in response to different stresses in S. cerevisiae. Taken together, a wide range of studies indicate that multiple elements act in concert to bring about appropriate translational responses. These include regulatory elements within mRNAs, altered mRNA interactions with RNA-binding proteins and the specialization of ribosomes that each contribute towards regulating protein expression to suit the changing environmental conditions.

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Glucose-Regulated Phosphorylation of the PUF Protein Puf3 Regulates the Translational Fate of Its Bound mRNAs and Association with RNA Granules

Cited by 90 publications

References 55 publications

Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling

Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling

Functional and regulatory profiling of energy metabolism in fission yeast

Translational regulation in response to stress in Saccharomyces cerevisiae

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