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

Abstract

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. ...

The RNA-binding protein RGGA is a sugar-responsive cofactor of the 5'-3' exonuclease XRN4 that post-transcriptionally meditates plant growth

“…This echoes previous demonstrations that AtXRN4's recognition of a subset of mRNAs under thermal stress requires help from the RNA-binding protein AtLARP1 (Merret et al, 2013). Notably, the yeast RNA-binding protein VTS1 was shown to function in glucose-induced mRNA decay (Braun et al, 2016). Viewed together, these results clearly indicate that the speci city of XRN-mediated RNA decay is mediated by particular RNA-binding cofactor proteins.…”

Promoter architecture determines cotranslational regulation of mRNA

“…To further complicate the relationship between sequence and expression, some transcription factors (TFs) influence mRNA stability and localization (Bregman et al 2011;Zid and O'Shea 2014;Braun et al 2015). Thus, in addition to affecting mRNA synthesis rates, promoters play a role in other parts in the life of an mRNA.…”

Systematic identification of factors mediating accelerated mRNA degradation in response to changes in environmental nitrogen

“…For example, the RNA-binding protein (RBP) Puf3p recognizes a cis -element in 3’ UTRs [ 38 ] and affects mRNA degradation rates depending on Puf3p phosphorylation status [ 39 ]. In addition to cis -elements within the transcript, promoters have been shown to mark certain RNA-protein (RNP) complexes to specify their post-transcriptional regulation [ 17 , 40 – 42 ]. These mechanisms may be controlled by a variety of different signalling pathways including Snf1 [ 43 , 44 ], PKA [ 45 ], Phk1/2 [ 46 ], and TORC1 [ 47 ].…”