The role of stress-activated RNA–protein granules in surviving adversity

Escalante, Leah E.; Gasch, Audrey P.

doi:10.1261/rna.078738.121

Cited by 20 publications

(11 citation statements)

References 128 publications

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“…As anticipated, Drosophila S2 cells acutely exposed to the well-known stressor sodium arsenite show robust formation of Ataxin-2 and Rasputin (Rin)/Ras GTPase-activating protein-binding protein 1 (G3BP1) positive SGs along with simultaneous inhibition of global translation (Escalante and Gasch, 2021;Ivanov et al, 2019;Jain et al, 2016;Kedersha et al, 2016;Kedersha and Anderson, 2007;Wheeler et al, 2016). Parallel RNA-seq analyses show that arsenite stress also induces upregulation of around 300 different transcripts.…”

Section: Introductionmentioning

confidence: 60%

The Transcriptional Response to Oxidative Stress Is Independent of Stress-Granule Formation

Singh

Kandi

Jayaprakashappa

et al. 2021

Preprint

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Cells respond to stress with translational arrest, robust transcriptional changes, and transcription-independent formation of mRNP assemblies termed stress granules (SGs). Despite considerable interest in the role of SGs in oxidative, unfolded-protein, and viral stress responses, whether and how SGs contribute to stress-induced transcription has not been rigorously examined. To address this issue, we characterized transcriptional changes in Drosophila S2 cells induced by acute oxidative-stress and assessed how these were altered under conditions that disrupted SG assembly. Sodium-arsenite stress for 3 hours predominantly resulted in the induction or upregulation of stress-responsive mRNAs whose levels peaked during cell recovery after stress cessation. The stress-transcriptome is enriched in mRNAs coding for protein chaperones, including HSP70 and low molecular-weight heat shock proteins, glutathione transferases, and several non-coding RNAs. Oxidative stress also induced prominent cytoplasmic stress granules that disassembled 3-hours after stress cessation. As expected, RNAi-mediated knockdown of the conserved G3BP1/ Rasputin protein inhibited stress-granule assembly. However, this disruption had no significant effect on the stress-induced transcriptional response or stress-induced translational arrest. Thus, SG assembly and stress-induced effects on gene expression appear to be driven by distinctive signaling processes. We suggest that while SG assembly represents a fast, transient mechanism, the transcriptional response enables a slower, longer-lasting mechanism for adaptation to and recovery from cell stress.

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Section: Introductionmentioning

confidence: 60%

The Transcriptional Response to Oxidative Stress Is Independent of Stress-Granule Formation

Singh

Kandi

Jayaprakashappa

et al. 2021

Preprint

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“…While P-bodies and stress granules share important similarities, there are stress-specific differences in composition and assembly ( 75 , 76 ). Typically, they are viewed as storage sites of translationally repressed mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Determinants of the temperature adaptation of mRNA degradation

Jaquet

Wallerich

Voegeli

et al. 2022

Nucleic Acids Research

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The rate of chemical reactions increases proportionally with temperature, but the interplay of biochemical reactions permits deviations from this relation and adaptation. The degradation of individual mRNAs in yeast increased to varying degrees with temperature. We examined how these variations are influenced by the translation and codon composition of mRNAs. We developed a method that revealed the existence of a neutral half-life above which mRNAs are stabilized by translation but below which they are destabilized. The proportion of these two mRNA subpopulations remained relatively constant under different conditions, even with slow cell growth due to nutrient limitation, but heat shock reduced the proportion of translationally stabilized mRNAs. At the same time, the degradation of these mRNAs was partially temperature-compensated through Upf1, the mediator of nonsense-mediated decay. Compensation was also promoted by some asparagine and serine codons, whereas tyrosine codons promote temperature sensitization. These codons play an important role in the degradation of mRNAs encoding key cell membrane and cell wall proteins, which promote cell integrity.

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“…For example, in yeast experiencing nutrient starvation or heat shock, PKA subunits can be sequestered in phase-separated granules including P-bodies (PB) and stress granules (SG) ( Tudisca et al, 2010 ). These granules comprise RNA-modulating enzymes including decay factors or translational regulators, for PB and SG, respectively, and mRNAs that tend to be translationally repressed (reviewed in Luo et al, 2018 ; Escalante and Gasch, 2021 ). There is some evidence that PKA is involved in the formation of PB and SG during stress ( Ramachandran et al, 2011 ), and it is possible that active PKA is localized there, as seen for other kinases ( Emperador-Melero et al, 2021 ).…”

Section: Specificity and Heterogeneity In Pka Functionmentioning

confidence: 99%

Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses

Kocik

Gasch

2022

Front. Cell Dev. Biol.

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Protein Kinase A (PKA) is an essential kinase that is conserved across eukaryotes and plays fundamental roles in a wide range of organismal processes, including growth control, learning and memory, cardiovascular health, and development. PKA mediates these responses through the direct phosphorylation of hundreds of proteins–however, which proteins are phosphorylated can vary widely across cell types and environmental cues, even within the same organism. A major question is how cells enact specificity and precision in PKA activity to mount the proper response, especially during environmental changes in which only a subset of PKA-controlled processes must respond. Research over the years has uncovered multiple strategies that cells use to modulate PKA activity and specificity. This review highlights recent advances in our understanding of PKA signaling control including subcellular targeting, phase separation, feedback control, and standing waves of allosteric regulation. We discuss how the complex inputs and outputs to the PKA network simultaneously pose challenges and solutions in signaling integration and insulation. PKA serves as a model for how the same regulatory factors can serve broad pleiotropic functions but maintain specificity in localized control.

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The role of stress-activated RNA–protein granules in surviving adversity

Cited by 20 publications

References 128 publications

The Transcriptional Response to Oxidative Stress Is Independent of Stress-Granule Formation

The Transcriptional Response to Oxidative Stress Is Independent of Stress-Granule Formation

Determinants of the temperature adaptation of mRNA degradation

Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses

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