Transient intracellular acidification regulates the core transcriptional heat shock response

Triandafillou, Catherine G.; Katanski, Christopher D.; Dinner, Aaron R.; Drummond, D. Allan

doi:10.7554/elife.54880

Cited by 65 publications

(50 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A decrease in intracellular pH has been suggested to underlie the response of yeast cells to multiple stresses ( Dechant et al., 2014 ; García et al., 2017 ; Munder et al., 2016 ; Triandafillou et al., 2020 ). We therefore tested the effects of sorbic acid, a protonophore that equilibrates the cytosolic and extracellular pH.…”

Section: Resultsmentioning

confidence: 99%

Stress-Induced Translation Inhibition through Rapid Displacement of Scanning Initiation Factors

et al. 2020

View full text Add to dashboard Cite

Summary Cellular responses to environmental stress are frequently mediated by RNA-binding proteins (RBPs). Here, we examined global RBP dynamics in Saccharomyces cerevisiae in response to glucose starvation and heat shock. Each stress induced rapid remodeling of the RNA-protein interactome without corresponding changes in RBP abundance. Consistent with general translation shutdown, ribosomal proteins contacting the mRNA showed decreased RNA association. Among translation components, RNA association was most reduced for initiation factors involved in 40S scanning (eukaryotic initiation factor 4A [eIF4A], eIF4B, and Ded1), indicating a common mechanism of translational repression. In unstressed cells, eIF4A, eIF4B, and Ded1 primarily targeted the 5′ ends of mRNAs. Following glucose withdrawal, 5′ binding was abolished within 30 s, explaining the rapid translation shutdown, but mRNAs remained stable. Heat shock induced progressive loss of 5′ RNA binding by initiation factors over ∼16 min and provoked mRNA degradation, particularly for translation-related factors, mediated by Xrn1. Taken together, these results reveal mechanisms underlying translational control of gene expression during stress.

show abstract

Section: Resultsmentioning

confidence: 99%

Stress-Induced Translation Inhibition through Rapid Displacement of Scanning Initiation Factors

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Ola1p and Ola1p GFP were purified from insect cells ( Figure S2c ) and studied in buffers of varying pH to mimic the cytosolic pH changes of yeast cells during heat shock. Under non-stress conditions, the cytosolic pH of yeast cells is close to 7.5 and acidifies to values between 6.5 and 7.0 during heat shock (35, 36). Using microscopy, we observed no assembled forms of Ola1p in pH 6.0-7.5 buffers at a concentration of 2.5 µM, which reflects its cellular concentration (for details on the calculation, see the Methods section), whereas it formed assemblies resembling small spherical clusters that grow up to more than 10 µm in size upon increasing the temperature to 42°C ( Figure 3e ).…”

Section: Resultsmentioning

confidence: 99%

Quantitative proteomics identifies the universally conserved ATPase Ola1p as a positive regulator of heat shock response in Saccharomyces cerevisiae

Dannenmaier

Altamirano

Schueler

et al. 2021

Preprint

View full text Add to dashboard Cite

The universally conserved P-loop ATPase Ola1 is implicated in various cellular stress response pathways, as well as in cancer and tumor progression. However, Ola1p functions are divergent between species and the involved mechanisms are only poorly understood. Here, we studied the role of Ola1p in the heat shock response of the yeast Saccharomyces cerevisiae using a combination of quantitative and pulse labeling-based proteomics approaches, in vitro studies and cell-based assays. Our data show that when heat stress is applied to cells lacking Ola1p, the expression of stress-protective proteins is enhanced. During heat stress Ola1p associates with detergent-resistant protein aggregates and rapidly forms assemblies that localize to stress granules. The assembly of Ola1p was also observed in vitro using purified protein and conditions, which resembled those in living cells. We show that loss of Ola1p results in increased protein ubiquitination of detergent-insoluble aggregates recovered from heat-shocked cells. When subsequently cells lacking Ola1p were relieved from heat stress, reinitiation of translation was delayed, whereas, at the same time, de novo synthesis of central factors required for protein refolding and the clearance of aggregates was enhanced when compared to wildtype cells. The combined data suggest that upon acute heat stress, Ola1p is involved in the stabilization of misfolded proteins, which become sequestered in cytoplasmic stress granules. This function of Ola1p enables cells to resume translation in a timely manner as soon as heat stress is relieved.

show abstract

“…Moreover changes in pHi can regulate metabolism (4,5), proliferation (6), and cell fate (7), among other processes. Intriguingly, stress-associated intracellular acidification appears to be broadly conserved, suggesting that a drop in pHi is a primordial mechanism to coordinate the general cellular stress response (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…These genes are referred to as "glucose-repressed genes", as they are transcriptionally repressed in the presence of glucose (20,21). Recently, evidence was presented of a positive role for acidic pHi in stress-gene induction: transient acidification is required for induction of the transcriptional heat-shock response in some conditions (13). However, the molecular mechanisms by which the transcriptional machinery senses and responds to pH changes remain mysterious.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SWI/SNF senses carbon starvation with a pH-sensitive low complexity sequence

Gutiérrez¹,

Brittingham²,

Karadeniz³

et al. 2021

Preprint

View full text Add to dashboard Cite

It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in S. cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. We found that a glutamine-rich low complexity sequence (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming during carbon starvation. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to a model promoter in vitro. Simulations showed that protonation of histidines within the SNF5 QLC lead to conformational expansion, providing a potential biophysical mechanism for regulation of these interactions. Together, our results indicate that that pH changes are a second messenger for transcriptional reprogramming during carbon starvation, and that the SNF5 QLC acts as a pH-sensor.

show abstract

Transient intracellular acidification regulates the core transcriptional heat shock response

Cited by 65 publications

References 99 publications

Stress-Induced Translation Inhibition through Rapid Displacement of Scanning Initiation Factors

Stress-Induced Translation Inhibition through Rapid Displacement of Scanning Initiation Factors

Quantitative proteomics identifies the universally conserved ATPase Ola1p as a positive regulator of heat shock response in Saccharomyces cerevisiae

SWI/SNF senses carbon starvation with a pH-sensitive low complexity sequence

Contact Info

Product

Resources

About