Glycolytic flux in <i>Saccharomyces cerevisiae</i> is dependent on RNA polymerase III and its negative regulator Maf1

Szatkowska, Roza; Garcia-Albornoz, Manuel; Roszkowska, Katarzyna; Holman, Stephen W.; Furmanek, Emil; Hubbard, Simon J.; Beynon, Robert J.; Adamczyk, M.

doi:10.1042/bcj20180701

Cited by 14 publications

(30 citation statements)

References 146 publications

(192 reference statements)

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“…For example, in yeast reduced Pol III activity is associated with de novo amino acid synthesis, a decreased abundance of glycolytic enzymes and reduced glycolytic flux. In contrast, in the same study enhanced glycolytic flux was observed in Maf1-deficient yeast cells ( Cieśla et al, 2007 ; Szatkowska et al, 2019 ), with evidence of greater hepatic glycolytic flux in fed Maf1 KO mice ( Willis et al, 2018 ). Thus, taken together there are several candidate mechanisms via which Pol III inhibition may act to increase lifespan and healthspan.…”

Section: Mechanisms Of Longevity Incurred By Pol III Inhibitionmentioning

confidence: 74%

RNA Polymerase III, Ageing and Longevity

et al. 2021

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Transcription in eukaryotic cells is performed by three RNA polymerases. RNA polymerase I synthesises most rRNAs, whilst RNA polymerase II transcribes all mRNAs and many non-coding RNAs. The largest of the three polymerases is RNA polymerase III (Pol III) which transcribes a variety of short non-coding RNAs including tRNAs and the 5S rRNA, in addition to other small RNAs such as snRNAs, snoRNAs, SINEs, 7SL RNA, Y RNA, and U6 spilceosomal RNA. Pol III-mediated transcription is highly dynamic and regulated in response to changes in cell growth, cell proliferation and stress. Pol III-generated transcripts are involved in a wide variety of cellular processes, including translation, genome and transcriptome regulation and RNA processing, with Pol III dys-regulation implicated in diseases including leukodystrophy, Alzheimer’s, Fragile X-syndrome and various cancers. More recently, Pol III was identified as an evolutionarily conserved determinant of organismal lifespan acting downstream of mTORC1. Pol III inhibition extends lifespan in yeast, worms and flies, and in worms and flies acts from the intestine and intestinal stem cells respectively to achieve this. Intriguingly, Pol III activation achieved through impairment of its master repressor, Maf1, has also been shown to promote longevity in model organisms, including mice. In this review we introduce the Pol III transcription apparatus and review the current understanding of RNA Pol III’s role in ageing and lifespan in different model organisms. We then discuss the potential of Pol III as a therapeutic target to improve age-related health in humans.

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Section: Mechanisms Of Longevity Incurred By Pol III Inhibitionmentioning

confidence: 74%

RNA Polymerase III, Ageing and Longevity

et al. 2021

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“…Here, we show that the binding of tRNAs to GAPDH is regulated by Maf1. Earlier work identified regulatory interactions between carbon metabolism enzymes and Pol III activity (Ciesla et al2007, Morawiec et al2013, Szatkowska et al2019), but fell short of noticing the direct and carbon source-dependent interaction of glycolytic enzymes with Pol III transcripts. Our findings may indicate a critical link between nutrient availability, energy metabolism and Pol III activity (Figure 6B).…”

Section: Discussionmentioning

confidence: 99%

Small non-coding RNA Interactome Capture reveals pervasive, carbon source-dependent tRNA engagement of yeast glycolytic enzymes

Asencio

Schwarzl

Sahadevan

et al. 2022

Preprint

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Small non-coding RNAs fulfill key functions in cellular and organismal biology, typically working in concert with RNA-binding proteins (RBPs). While proteome-wide methodologies have enormously expanded the repertoire of known RBPs, these methods do not distinguish RBPs binding to small non-coding RNAs from the rest. To specifically identify this relevant subclass of RBPs, we developed small non-coding RNA interactome capture (snRIC2C) based on the differential RNA-binding capacity of silica matrices (2C). We define the S. cerevisiae proteome of nearly 300 proteins that specifically binds to RNAs smaller than 200 nucleotides in length (snRBPs), identifying informative distinctions from the total RNA-binding proteome determined in parallel. Strikingly, the snRBPs include most glycolytic enzymes from yeast. With further methodological developments using silica matrices, 12 tRNAs were identified as specific binders of the glycolytic enzyme GAPDH. We show that tRNA engagement of GAPDH is carbon source-dependent and regulated by the RNA polymerase III repressor Maf1, suggesting a regulatory interaction between glycolysis and RNA polymerase III activity. We conclude that snRIC2C and other 2C-derived methods greatly facilitate the study of RBPs, revealing previously unrecognised interactions.

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“…Furthermore, glycolysis performance is related to enzyme abundance, cell fermentative activity, and proliferation. Under the regulation of Maf1, Snf1, and other proteins according to the external growth environment, yeast can change the metabolism of amino acids, proteins, and other substances through the glycolysis pathway, and regulates the transformation between respiration and fermentation metabolism 25,26 . The TCA cycle is the main mode of respiratory metabolism in mitochondria and shares a pyruvate precursor with ethanol metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…Under the regulation of Maf1, Snf1, and other proteins according to the external growth environment, yeast can change the metabolism of amino acids, proteins, and other substances through the glycolysis pathway, and regulates the transformation between respiration and fermentation metabolism. 25,26 The TCA cycle is the main mode of respiratory metabolism in mitochondria and shares a pyruvate precursor with ethanol metabolism. TCA cycle and glycolysis are two different carbon metabolic pathways, which are the main sources of yeast energy.…”

Section: Introductionmentioning

confidence: 99%

Effect of glucose levels on carbon flow rate, antioxidant status, and enzyme activity of yeast during fermentation

2022

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BACKGROUND:The physiological metabolism of yeast has a significant impact on the quality of fermentation products. The present study aimed to investigate yeast metabolism in response to a changing glucose content environment, especially in fermentation products, as well as the change of carbon flow rate, antioxidant status, and yeast enzyme activity. RESULTS: Yeast in a 0 g L −1 glucose level was subjected to carbon starvation stress, cell growth retardation and cell proliferation was significantly inadequate; in the logarithmic growth stage of yeast, at a 30 g L −1 glucose level, the carbon source mainly flowed to tricarboxylic acid cycle and pentose phosphate metabolism, cell division, proliferation, and increased cell growth. In later logarithmic growth period and stable period, carbon flowed into glycerol and trehalose metabolism, to cope with the environmental stress; yeast in 60 and 150 g L −1 glucose levels faced high glucose stress at the beginning, the content of reactive oxygen increased, malondialdehyde content increased, cell damage was reduced through the regulation of superoxide dismutase and catalase enzyme activities, and most of the carbon flowed into the metabolic pathway of ethanol, glycerol, and trehalose to cope with high glucose stress, the pentose phosphate pathway showed a large late influx, and NADPH also started to increase rapidly after 24 h. CONCLUSION: Yeast was stressed in a high-sugar environment and ensured the activity of yeast by preferentially increasing the metabolic intensity of trehalose, glycerol, and glycolytic metabolism, weakening tricarboxylic acid metabolism, and first weakening and then increasing pentose phosphate metabolism.

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Glycolytic flux in Saccharomyces cerevisiae is dependent on RNA polymerase III and its negative regulator Maf1

Cited by 14 publications

References 146 publications

RNA Polymerase III, Ageing and Longevity

RNA Polymerase III, Ageing and Longevity

Small non-coding RNA Interactome Capture reveals pervasive, carbon source-dependent tRNA engagement of yeast glycolytic enzymes

Effect of glucose levels on carbon flow rate, antioxidant status, and enzyme activity of yeast during fermentation

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