The sweet side of<scp>RNA</scp>regulation: glyceraldehyde‐3‐phosphate dehydrogenase as a noncanonical<scp>RNA</scp>‐binding protein

White, Michael R. H.; Garcin, Elsa D.

doi:10.1002/wrna.1315

Cited by 41 publications

(32 citation statements)

References 133 publications

(345 reference statements)

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“…Of the metabolic enzymes that can also bind mRNA, the best characterized is GAPDH, which has been shown to interact with numerous, different mRNAs and regulates their stability or efficiency of translation (reviewed in ref. 100 ). For some of these interactions, the effect of the catalytic activity of GAPDH on its non-canonical function as an mRNA-binding protein has not been addressed.…”

Section: Metabolic Enzymes As Rna Binding Proteinsmentioning

confidence: 99%

Non-canonical functions of enzymes facilitate cross-talk between cell metabolic and regulatory pathways

Snaebjornsson

Schulze

2018

Exp Mol Med

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The metabolic rewiring that occurs during cell transformation is a hallmark of cancer. It is diverse in different cancers as it reflects different combinations of oncogenic drivers, tumor suppressors, and the microenvironment. Metabolic rewiring is essential to cancer as it enables uncontrolled proliferation and adaptation to the fluctuating availability of nutrients and oxygen caused by poor access to the vasculature due to tumor growth and a foreign microenvironment encountered during metastasis. Increasing evidence now indicates that the metabolic state in cancer cells also plays a causal role in tumor growth and metastasis, for example through the action of oncometabolites, which modulate cell signaling and epigenetic pathways to promote malignancy. In addition to altering the metabolic state in cancer cells, some multifunctional enzymes possess non-metabolic functions that also contribute to cell transformation. Some multifunctional enzymes that are highly expressed in cancer, such as pyruvate kinase M2 (PKM2), have non-canonical functions that are co-opted by oncogenic signaling to drive proliferation and inhibit apoptosis. Other multifunctional enzymes that are frequently downregulated in cancer, such as fructose-bisphosphatase 1 (FBP1), are tumor suppressors, directly opposing mitogenic signaling via their non-canonical functions. In some cases, the enzymatic and non-canonical roles of these enzymes are functionally linked, making the modulation of non-metabolic cellular processes dependent on the metabolic state of the cell.

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Section: Metabolic Enzymes As Rna Binding Proteinsmentioning

confidence: 99%

Non-canonical functions of enzymes facilitate cross-talk between cell metabolic and regulatory pathways

Snaebjornsson

Schulze

2018

Exp Mol Med

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“…Numerous publications investigating the S-sulfhydration of GAPDH and its regulation have been highlighted in recent years due to the importance of this protein in diverse biological functions, in addition to its classical glycolytic role. These include its participation in mRNA regulation, DNA replication, endocytosis or regulation of apoptosis (Sirover 2011, Henry et al 2015, White and Garcin 2016. Mammalian GAPDH was first described as an S-sulfhydrated protein at Cys150 and this modification results in an increase in enzymatic activity in mice (Mustafa et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Regulates the Cytosolic/Nuclear Partitioning of Glyceraldehyde-3-Phosphate Dehydrogenase by Enhancing its Nuclear Localization

Aroca

Schneider

Scheibe

et al. 2017

Plant and Cell Physiology

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Hydrogen sulfide is an important signaling molecule comparable with nitric oxide and hydrogen peroxide in plants. The underlying mechanism of its action is unknown, although it has been proposed to be S-sulfhydration. This post-translational modification converts the thiol groups of cysteines within proteins to persulfides, resulting in functional changes of the proteins. In Arabidopsis thaliana, Ssulfhydrated proteins have been identified, including the cytosolic isoforms of glyceraldehyde-3-phosphate dehydrogenase GapC1 and GapC2. In this work, we studied the regulation of sulfide on the subcellular localization of these proteins using two different approaches. We generated GapC1-green fluorescent protein (GFP) and GapC2-GFP transgenic plants in both the wild type and the des1 mutant defective in the L-cysteine desulfhydrase DES1, responsible for the generation of sulfide in the cytosol. The GFP signal was detected in the cytoplasm and the nucleus of epidermal cells, although with reduced nuclear localization in des1 compared with the wild type, and exogenous sulfide treatment resulted in similar signals in nuclei in both backgrounds. The second approach consisted of the immunoblot analysis of the GapC endogenous proteins in enriched nuclear and cytosolic protein extracts, and similar results were obtained. A significant reduction in the total amount of GapC in des1 in comparison with the wild type was determined and exogenous sulfide significantly increased the protein levels in the nuclei in both plants, with a stronger response in the wild type. Moreover, the presence of an Ssulfhydrated cysteine residue on GapC1 was demonstrated by mass spectrometry. We conclude that sulfide enhances the nuclear localization of glyceraldehyde-3-phosphate dehydrogenase.

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“…From proteomics, Tdh activity was slightly lower in rpc128-1007 cells under the same growth conditions, but Tdh activity measured in rpc128-1007 grown on glycerol was significantly lower when compared to the reference strain, which suggests that the catalytic activity of the enzyme decreases in vivo while the enzyme converts 1,3-bisphosphoglycerate (1,3-BPG) into glyceraldehydes-3-phosphate (G3P) in the reverse direction to glycolysis, when the enzymes is involved in gluconeogenesis in the presence of non-fermentable carbon sources in the medium. This shuttle between the cytosol and the nucleus linking metabolic redox status to gene transcription [65] and contributes to tRNA transport [66].…”

Section: Resultsmentioning

confidence: 99%

Glycolytic flux inSaccharomyces cerevisiaeis dependent on RNA polymerase III and its negative regulator Maf1

Szatkowska

Garcia-Albornoz

Roszkowska

et al. 2018

Preprint

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Protein biosynthesis is energetically costly, is tightly regulated and is coupled to stress conditions including glucose deprivation. RNA polymerase III (RNAP III) driven transcription of tDNA genes for production of tRNAs is a key element in efficient protein biosynthesis. Here we present an analysis of the effects of altered RNAP III activity on the Saccharomyces cerevisiae proteome and metabolism under glucose rich conditions. We show for the first time that RNAP III is tightly coupled to the glycolytic system at the molecular systems level. Decreased RNAP III activity or the absence of the RNAP III negative regulator, Maf1 elicit broad changes in the abundance profiles of enzymes engaged in fundamental metabolism in S. cerevisiae. In a mutant compromised in RNAP III activity there is a repartitioning towards amino acids synthesis de novo at the expense of glycolytic throughput. Conversely, cells lacking Maf1 protein have greater potential for glycolytic flux.

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The sweet side ofRNAregulation: glyceraldehyde‐3‐phosphate dehydrogenase as a noncanonicalRNA‐binding protein

Cited by 41 publications

References 133 publications

Non-canonical functions of enzymes facilitate cross-talk between cell metabolic and regulatory pathways

Non-canonical functions of enzymes facilitate cross-talk between cell metabolic and regulatory pathways

Hydrogen Sulfide Regulates the Cytosolic/Nuclear Partitioning of Glyceraldehyde-3-Phosphate Dehydrogenase by Enhancing its Nuclear Localization

Glycolytic flux inSaccharomyces cerevisiaeis dependent on RNA polymerase III and its negative regulator Maf1

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