Snf1p Regulates Gcn5p Transcriptional Activity by Antagonizing Spt3p

Liu, Yang; Xu, Xinjing; Kuo, Min Hao

doi:10.1534/genetics.109.110957

Cited by 27 publications

(23 citation statements)

References 89 publications

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“…Xrn1 might be one such protein, because it is found in the nucleus (92; but see reference 59 for a conflicting report) and its activity appears to be regulated by Snf1-dependent phosphorylation (27). Although the known nuclear role of AMPK and Snf1 is to modify chromatin through activation of histone acetyltransferases (89,90,93), they could also influence posttranscriptional gene regulation by one of the mechanisms described above.…”

Section: Discussionmentioning

confidence: 99%

Snf1-Dependent Transcription Confers Glucose-Induced Decay upon the mRNA Product

Braun

Dombek

Young

2016

Molecular and Cellular Biology

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In the yeast Saccharomyces cerevisiae, the switch from respiratory metabolism to fermentation causes rapid decay of transcripts encoding proteins uniquely required for aerobic metabolism. Snf1, the yeast ortholog of AMP-activated protein kinase, has been implicated in this process because inhibiting Snf1 mimics the addition of glucose. In this study, we show that the SNF1-dependent ADH2 promoter, or just the major transcription factor binding site, is sufficient to confer glucose-induced mRNA decay upon heterologous transcripts. SNF1-independent expression from the ADH2 promoter prevented glucose-induced mRNA decay without altering the start site of transcription. SNF1-dependent transcripts are enriched for the binding motif of the RNA binding protein Vts1, an important mediator of mRNA decay and mRNA repression whose expression is correlated with decreased abundance of SNF1-dependent transcripts during the yeast metabolic cycle. However, deletion of VTS1 did not slow the rate of glucose-induced mRNA decay. ADH2 mRNA rapidly dissociated from polysomes after glucose repletion, and sequences bound by RNA binding proteins were enriched in the transcripts from repressed cells. Inhibiting the protein kinase A pathway did not affect glucose-induced decay of ADH2 mRNA. Our results suggest that Snf1 may influence mRNA stability by altering the recruitment activity of the transcription factor Adr1. T he regulation of gene expression by nutritional conditions inSaccharomyces cerevisiae yeast, particularly the availability of glucose, has been a paradigm of transcriptional control (1-7). Glucose deprivation leads to a global reorganization of transcription (8). Numerous genes are upregulated to allow the cell to switch to a respiratory mode of metabolism, and a large number of genes are downregulated as the cells adapt to a lower rate of growth. Snf1, the yeast ortholog of AMP-activated protein kinase (AMPK) (6), is responsible for upregulating the expression of over 400 genes after glucose depletion (9). Snf1, together with the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and target of rapamycin (TOR) pathways, coordinates many of the nutrientresponsive metabolic pathways in yeast (10). Despite the preponderance of evidence indicating altered transcription as the major factor determining the increase in mRNA abundance when yeast cells are depleted of glucose, there is considerable evidence indicating that posttranscriptional changes, particularly an increase in mRNA stability, are also important in determining gene expression levels (11)(12)(13)(14)(15). A recent study demonstrated that promoter sequences influence the subcellular location and efficiency of translation of transcripts upregulated by glucose starvation (16). Thus, promoter sequences appear to have a role in gene expression that includes both transcriptional and posttranscriptional processes.Glucose-induced mRNA decay is a process that leads to rapid loss of mRNAs encoding enzymes required for efficient aerobic respiration when glucose is replenished. ...

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Section: Discussionmentioning

confidence: 99%

Snf1-Dependent Transcription Confers Glucose-Induced Decay upon the mRNA Product

Braun

Dombek

Young

2016

Molecular and Cellular Biology

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“…Interestingly, the Snf1 protein kinase was shown to drive histone acetylation at the INO1 promoter [18], and more recently to regulate Gcn5 transcriptional activity [19]. Nevertheless, a direct involvement of Snf1 in the control of chromatin structure has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

“…Mechanisms of transcriptional control include phosphorylation and translocation of the Mig1 repressor [10,11], interaction with the activator Sip4 [12], phosphorylation and activation of Cat8 [13,14], regulation of the binding of the activator Adr1 [15], and interaction with the transcriptional apparatus [16,17]. Moreover, Snf1 was shown to have a role in histone acetylation at the INO1 promoter [18], although this finding is controversial [17], and recent evidence underlines direct regulation of Gcn5 transcriptional activity [19]. …”

Section: Introductionmentioning

confidence: 99%

Snf1/AMPK regulates Gcn5 occupancy, H3 acetylation and chromatin remodelling at S. cerevisiae ADY2 promoter

Abate

Bastonini

Braun

et al. 2012

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The ability of cells to respond to changes in their environment is mediated by transcription factors that remodel chromatin and reprogram expression of specific subsets of genes. In Saccharomyces cerevisiae, changes in carbon source lead to gene induction by Adr1 and Cat8 that are known to require the upstream function of the Snf1 protein kinase, the central regulator of carbon metabolism, to exert their activating effect. How Snf1 facilitates transcription activation by Adr1 and Cat8 is not known. Here we show that under derepressing conditions, deletion of SNF1 abolishes the increase of histone H3 acetylation at the promoter of the glucose-repressed ADY2 gene, and as a consequence profoundly affects the chromatin structural alterations accompanying transcriptional activation. Adr1 and Cat8 are not required to regulate the acetylation switch and show only a partial influence on chromatin remodelling at this promoter, though their double deletion completely abolishes mRNA accumulation. Finally, we show that under derepressing conditions the recruitment of the histone acetyltransferase Gcn5 is abolished by SNF1 deletion, possibly explaining the lack of increased histone H3 acetylation and nucleosome remodelling. The results highlight a mechanism by which signalling to chromatin provides an essential permissive signal that is required for activation by glucose-responsive transcription factors.

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“…An important goal for future work will be to determine how GCN5 senses the lack of nutrients and becomes activated. In budding yeast, GCN5 is phosphorylated by AMPK, which in turn promotes expression of GCN5 target genes (35). In the atrophying muscles where p65K310 acetylation is induced, phosphorylated AMPK was elevated (Fig.…”

Section: Volume 290 • Number 51 • December 18 2015mentioning

confidence: 96%

Muscle Wasting in Fasting Requires Activation of NF-κB and Inhibition of AKT/Mechanistic Target of Rapamycin (mTOR) by the Protein Acetylase, GCN5

Lee

Goldberg

2015

Journal of Biological Chemistry

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NF-B is best known for its pro-inflammatory and anti-apoptotic actions, but in skeletal muscle, NF-B activation is important for atrophy upon denervation or cancer. Here, we show that also upon fasting, NF-B becomes activated in muscle and is critical for the subsequent atrophy. Following food deprivation, the expression and acetylation of the p65 of NF-B on lysine 310 increase markedly in muscles. NF-B inhibition in mouse muscles by overexpression of the IB␣ superrepressor (IB␣-SR) or of p65 mutated at Lys-310 prevented atrophy. Knockdown of GCN5 with shRNA or a dominant-negative GCN5 or overexpression of SIRT1 decreased p65K310 acetylation and muscle wasting upon starvation. In addition to reducing atrogene expression, surprisingly inhibiting NF-B with IB␣-SR or by GCN5 knockdown in these muscles also enhanced AKT and mechanistic target of rapamycin (mTOR) activities, which also contributed to the reduction in atrophy. These new roles of NF-B and GCN5 in regulating muscle proteolysis and AKT/ mTOR signaling suggest novel approaches to combat muscle wasting.

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Snf1p Regulates Gcn5p Transcriptional Activity by Antagonizing Spt3p

Cited by 27 publications

References 89 publications

Snf1-Dependent Transcription Confers Glucose-Induced Decay upon the mRNA Product

Snf1-Dependent Transcription Confers Glucose-Induced Decay upon the mRNA Product

Snf1/AMPK regulates Gcn5 occupancy, H3 acetylation and chromatin remodelling at S. cerevisiae ADY2 promoter

Muscle Wasting in Fasting Requires Activation of NF-κB and Inhibition of AKT/Mechanistic Target of Rapamycin (mTOR) by the Protein Acetylase, GCN5

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