The stress granule transcriptome reveals principles of mRNA accumulation in stress granules.
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE99304
PROVIDER: PRJNA388080 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Stress granules are mRNA-protein assemblies formed on nontranslating mRNAs. Stress granules are important in the stress response, related to neuronal mRNP granules, and aberrant stress granules contribute to some degenerative diseases. By RNA-Seq and single molecule FISH, we describe the stress granule transcriptome in both yeast and mammalian cells. This reveals that while essentially every mRNA, and some ncRNAs, can be targeted to stress granules, the efficiency of targeting can vary from <1% to 73%. mRNA accumulation in stress granules is increased by longer coding regions, poor translatability, and correlates with some RNA binding proteins. Standardizing the RNA-Seq analysis by single molecule FISH allows a quantitative description of the general and stress granule transcriptome. Approximately 15% of the bulk mRNA molecules accumulate in stress granules suggesting their effect will be limited primarily to subsets of mRNAs highly accumulating in stress granules
2017-11-10 | GSE99304 | GEO
Project description:Ribonucleoprotein (RNP) granules are non-membrane bound organelles thought to assemble by protein-protein interactions of RNA-binding proteins. We present evidence that a wide variety of RNAs self-assemble in vitro into either liquid-liquid phase separations or more stable assembles, referred to as RNA tangles. Self-assembly in vitro is affected by RNA length, ionic conditions, and sequence. Remarkably, self-assembly of yeast RNA in vitro under physiological salt mimics the composition of mRNAs within yeast stress granules. This suggests that the biophysical principles that drive RNA self-assembly in vitro contribute to determining the stress granule transcriptome. Consistent with RNA self-assembly contributing to RNP granule formation, an excess of purified RNA injected into C. elegans syncytium coalesces into droplet-like assemblies. We suggest that diverse RNA-RNA interactions in trans contribute to RNP granule formation and may explain the prevalence of large RNA-protein assemblies in eukaryotic cells.
2017-05-23 | GSE99170 | GEO
Project description:We determined the enrichment of mRNA in stress granules in WT and NAT10 KO cells to assess the impact of RNA acetylation on stress granule mRNA localization.
2024-02-09 | GSE212380 | GEO
Project description:Stress granules are small RNA-protein granules that modify the translational landscape during cellular stress to promote survival. The RhoGTPase RhoA is implicated in the formation of RNA stress granules. Our data demonstrate that the cytokinetic proteins ECT2 and AurkB are localized to stress granules in human astrocytoma cells. AurkB and its downstream target histone-3 are phosphorylated during arsenite-induced stress. Chemical (AZD1152-HQPA) and siRNA inhibition of AurkB results in fewer and smaller stress granules when analyzed utilizing high throughput fluorescent based cellomics assays. RNA immunoprecipitation with the known stress granule aggregates TIAR and G3BP1 was performed on astrocytoma cells and subsequent analysis revealed that astrocytoma stress granules harbour unique mRNAs for various cellular pathways including cellular migration, metabolism, translation and transcriptional regulation. Human astrocytoma cell stress granules contain mRNA that are known to be involved in glioma signaling and the mTOR pathway. These data provide evidence that RNA stress granules are a novel form of epigenetic regulation in astrocytoma cells, which may be targetable by chemical inhibitors and enhance astrocytoma susceptiblity to conventional therapy such as radiation and chemotherapy. Astrocytoma cells were either untreated or treated with arsenite to induce stress granule formation and RNA immunoprecipitates were analyzed by exon array analysis. RNA species that were enriched in TIAR RIPs and G3BP1 RIPS, respectively were compared to compared to TIAR and G3BP1 RIPs from untreated cells and input controls. Ingenuity pathway analysis was performed on the stress granule enriched mRNAs from the TIAR and G3BP1 RIPs to identify significant functional biology networks.
2016-02-29 | E-GEOD-76814 | biostudies-arrayexpress
Project description:Stress granules are mRNA-protein assemblies formed from nontranslating mRNAs. Stress granules are important in the stress response and may contribute to some degenerative diseases. Here, we describe the stress granule transcriptome of yeast and mammalian cells through RNA-sequencing (RNA-seq) analysis of purified stress granule cores and single-molecule fluorescence in situ hybridization (smFISH) validation. While essentially every mRNA, and some noncoding RNAs (ncRNAs), can be targeted to stress granules, the targeting efficiency varies from <1% to >95%. mRNA accumulation in stress granules correlates with longer coding and UTR regions and poor translatability. Quantifying the RNA-seq analysis by smFISH reveals that only 10% of bulk mRNA molecules accumulate in mammalian stress granules and that only 185 genes have more than 50% of their mRNA molecules in stress granules. These results suggest that stress granules may not represent a specific biological program of messenger ribonucleoprotein (mRNP) assembly, but instead form by condensation of nontranslating mRNPs in proportion to their length and lack of association with ribosomes.
| S-EPMC5728175 | biostudies-literature
Project description:Stress granule and inflammasome assembly determine contrasting fates of stressed cells. FAM69C is a brain-enriched kinase associated with neurodegenerative diseases, but its biological functions are still largely unknown. Here we show that FAM69C plays an important role in the regulation of stress responses through promoting stress granule assembly and suppressing inflammasome activation. In response to ATP, a common inflammasome activator, mouse primary microglia, and BV-2 cells form stress granules. FAM69C deficiency hastens inflammasome activation in mouse microglia, which is accompanied by inhibited stress granule assembly. FAM69C promotes the assembly of stress granules and halts protein translation under stress. Aged Fam69c knockout mice show increased neuroinflammation and ASC specks formation. We further find that FAM69C physically phosphorylates eIF2α and promotes stress granule assembly. Our data reveal that FAM69C promotes stress granule assembly under stress and suppresses inflammasome formation in microglia, suggesting that FAM69C may be a potential therapeutic target for neurodegenerative diseases.
2022-10-05 | GSE214646 | GEO
Project description:The eukaryotic cytosol contains multiple RNP granules including P-bodies and stress granules. Three different methods have been used to describe the transcriptome of stress granules or P-bodies, but how these methods compare, and how RNA partitioning occurs between P-bodies and stress granules has not been addressed. Herein, we compare the analysis of the stress granule transcriptome based on differential centrifugation, with and without subsequent stress granule immunopurification. We find that while differential centrifugation alone gives a first approximation of the stress granule transcriptome, this methodology contains non-specific transcripts that play a confounding role in the interpretation of results. We also immunopurify and compare the RNAs in stress granules and P-bodies under arsenite stress and compare those results to the P-body transcriptome described under non-stress conditions. We find that the P-body transcriptome is dominated by poorly translated mRNAs under non-stress conditions, but during arsenite stress, when translation is globally repressed, the P-body transcriptome is very similar to the stress granule transcriptome. This suggests that translation is a dominant factor in targeting mRNAs into both P-bodies and stress granules, and during stress, when most mRNAs are untranslated, the composition of P- bodies reflects this broader translation repression.
2019-10-17 | GSE138988 | GEO
Project description:In this study we are examining the paracrine effect induced by feline calicivirus (FCV) infection on stress granule (SG) accumulation. We provided an understanding of paracrine granules function and specificity through their affinity purification followed RNAseq to systematically analyse their RNA content.
2022-02-09 | GSE171655 | GEO
Project description:Stress granules are phase separated assemblies formed around mRNAs that have now been identified after stress granule purification from cell culture. Here, we present a purification free method to detect stress granules RNAs in single cells and in tissues, including those displaying cell heterogeneity. We adapted TRIBE (Target of RNA-binding proteins Identified by Editing) to detect stress-granule RNAs by fusing a stress-granule RNA-binding protein (FMR1) to the catalytic domain of an RNA-editing enzyme (ADAR). RNAs colocalized with this fusion are edited, producing mutations that are detectable by sequencing. We then show that this “in situ" method can reliably identify stress granule RNAs in single S2 cells and in Drosophila neurons, and that they encode cell cycle, transcription and splicing factors. The identification of stress granule RNAs without perturbation opens the possibility to examine cell-to-cell variability and identify the RNA content not only in stress granules, but also in other RNA based assemblies in single cells derived from tissues.
2021-05-30 | GSE175782 | GEO
Project description:Stress granules are dynamic cytoplasmic ribonucleoprotein granules that assemble in response to cellular stress. Aberrant formation of stress granules has been linked to neurodegenerative diseases. However, the molecular mechanisms underlying the initiation of stress granules remain elusive. Here we report that the brain-enriched protein kinase FAM69C promotes stress granule assembly through phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). FAM69C physically interacts with eIF2α and functions as a stress-specific kinase for eIF2α, leading to stress-induced protein translation arrest and stress granule assembly. Primary microglia derived from Fam69c knockout mice exhibit aberrant stress granule assembly in response to oxidative stress and ATP. Defective stress granule assembly in microglia correlates with the formation of ASC specks and NLRP3 inflammasome activation, whereas induction of stress granule precludes inflammasome formation. Consistently, increased NLRP3 levels, caspase-1 cleavage and Il18 expression corroborate microglia-associated neuroinflammation in aged Fam69c knockout mice. Our study demonstrates that FAM69C is critical for stress granule assembly and suggests its role in the regulation of microglia function.
2023-04-21 | PXD037697 | Pride