Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA308648 | ENA |
REPOSITORIES: ENA
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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 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.
2016-02-29 | GSE76814 | GEO
Project description:N6-methyladenosine (m6A) in mRNA is key to eukaryotic gene regulation. Many m6A functions involve RNA-binding proteins that recognize m6A via a YT521-B Homology (YTH) domain. YTH domain proteins contain long intrinsically disordered regions (IDRs) that may mediate phase separation and interaction with protein partners, but whose precise biochemical functions remain largely unknown. The Arabidopsis thaliana YTH domain proteins ECT2, ECT3 and ECT4 accelerate organogenesis through stimulation of cell division in organ primordia. Here, we use ECT2 to reveal molecular underpinnings of this function. We show that stimulation of leaf formation requires the long N-terminal IDR, and we identify two short IDR-elements required for ECT2-mediated organogenesis. Of these two, a 19-amino acid region containing a tyrosine-rich motif conserved in both plant and metazoan YTHDF proteins is necessary for binding to the major cytoplasmic poly(A)-binding proteins PAB2, PAB4 and PAB8. Remarkably, overexpression of PAB4 in leaf primordia partially rescues the delayed leaf formation in ect2 ect3 ect4 mutants, suggesting that the ECT2-PAB2/4/8 interaction on target mRNAs of organogenesis-related genes may overcome limiting PAB concentrations in primordial cells.
2023-11-28 | PXD045801 | Pride
Project description:Abstract : "A hallmark of the cellular response to environmental stress is the formation of stress granules. Stress granules are RNA-protein assemblies that provide an adaptive response to stress; however, the basis for their formation and how they contribute to the stress response remains incompletely understood. Here we show that the mRNA modification N6-methyladenosine (m6A) is a mark that targets mRNAs to stress granules. We find that m6A mRNAs are highly enriched in stress granules, and this is mediated by m6A-induced liquid-liquid phase separation of the YTHDF family of m6A-binding proteins. These proteins bind poly-methylated m6A mRNAs, causing them to form liquid droplets that partition into stress granules. Moreover, disrupting either m6A or YTHDF proteins prevents stress granule formation." The goal of this experiment is to understand how recruitment of m6A mRNA to stress granules influences the translational response to heat shock. Result: we found that m6A-containing mRNA are preferentially repressed during stress, and that m6A is required for translational recovery after heat shock
2021-01-15 | GSE109253 | GEO
Project description:Alphaherpesviruses remodel the cellular transcriptome to deplete m6A-containing transcripts
| PRJNA827853 | ENA
Project description:Mitochondrial gene expression regulation is required for the biogenesis of oxidative phosphorylation (OXPHOS) complexes, yet the spatial organization of mitochondrial RNAs (mt-RNAs) remains unknown. Here, we investigated the spatial distribution of mt-RNAs during various cellular stresses using single-molecule RNA-FISH. We discovered that transcription inhibition leads to the formation of distinct RNA granules within mitochondria, which we term inhibition granules. These structures differ from canonical mitochondrial RNA granules (MRGs) and form in response to multiple transcription arrest conditions, including ethidium bromide treatment, specific inhibition of the mitochondrial RNA polymerase, and depletion of the SUV3 helicase. Inhibition granules appear to serve a protective function, stabilizing certain mt-mRNAs during prolonged transcription inhibition. This phenomenon coincides with an imbalance in OXPHOS complex expression, where mitochondrial-encoded transcripts decrease while nuclear-encoded subunits remain stable. We found that cells recover from transcription inhibition via resolving the granules, restarting transcription and repopulating the mitochondrial network with mt-mRNAs within hours. We suggest that inhibition granules may act as a reservoir to help overcome OXPHOS imbalance during recovery from transcription arrest.
2025-06-04 | GSE277754 | GEO
Project description:RNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule assembly and function in vivo remain unclear. In Xenopus laevis oocytes, maternal mRNAs are transported as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that vegetal transport RNPs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies are multiphase RNP granules, containing a dynamic liquid-like protein-containing phase surrounding a non-dynamic RNA-containing substructure. Our results support a role for RNA as a critical scaffold component within these RNP granules and suggest that cis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.
2020-09-20 | GSE158246 | GEO
Project description:Epithelial Cell Transforming Sequence 2 (ECT2), a guanine nucleotide exchange factor (GEF) for Rho GTPases, is overexpressed in many cancers and is involved in signal transduction pathways that promote cancer cell proliferation, invasion and tumorigenesis. Recently, we demonstrated that a significant pool of ECT2 localizes to the nucleolus of non small cell lung cancer (NSCLC) cells where it binds the transcription factor Upstream Binding Factor 1 (UBF1) on the promoter regions of the ribosomal DNA (rDNA) and activates rDNA transcription, transformed growth and tumor formation. Here we investigate the mechanism by which ECT2 engages UBF1 on rDNA. Mutagenesis of ECT2 demonstrates that the tandem BRCT domain of ECT2 mediates binding to UBF1. Biochemical and mass spectrometry analysis reveals that Protein Kinase Ci (PKCi) directly phosphorylates UBF1 at Ser412 to generate a phosphopeptide binding epitope that binds the ECT2 BRCT domain. Lentiviral shRNA knockdown and reconstitution experiments demonstrate that both a functional ECT2 BRCT domain and the UBF1 Ser412 phosphorylation site are required for UBF1 mediated ECT2 recruitment to rDNA, elevated rRNA synthesis and transformed growth. Taken together, our study provides new molecular insight into ECT2 mediated regulation of rDNA transcription in cancer cells and provides a rationale for therapeutic targeting of UBF1 and ECT2 stimulated rDNA transcription for the treatment of NSCLC.
2020-04-10 | MSV000085269 | MassIVE
Project description:Cells limit energy-consuming mRNA translation during stress to maintain metabolic homeostasis. Sequestration of mRNAs by RNA binding proteins (RBPs) into stress granules (SGs) reduces translation, but it remains unclear whether SGs also function in partitioning of specific transcripts to polysomes (PSs) to guide selective translation and stress-adaptation in cancer. Transcripts enriched in PSs, defined by polysome fractionation and RNAseq, were compared with mRNAs complexed with the SG-nucleator protein, G3BP1, defined by spatially-restricted enzymatic tagging. Short-term oxidative stress profoundly altered mRNA translation by promoting selective enrichment of transcripts within SGs or PSs. G3BP1 participates in this compartmentalisation by sequestering transcripts in SGs. Under stress, G3BP1-bound transcripts are PS-depleted and encode proteins involved in mRNA translation, pro-apoptosis, and mitochondrial function. In contrast, specific PS-enriched transcripts disassociate from G3BP1 under stress to encode proteins involved in diverse cellular cytoprotective pathways. Therefore, G3BP1 partitioning guides selective translation to support stress adaptation and cell survival.
2020-04-30 | PXD015491 | Pride
Project description:In cell stress, mRNA in the cytoplasm is sequestered to the insoluble ribonucleoprotein (RNP) compartments containing stress granules. These RNP granules are known to be involved in the control of mRNA processing and decay, but it has been elusive whether the mRNA redistribution in cell stress is universal or specific to a subset of transcripts. Here we provide a transcriptome-wide profiles of the RNP granules in cell stress and show that mRNA accumulation in stress granule differentially affects individual transcripts. mRNA species accumulated in stress granules are largely conserved across distinct stress types, such as in endoplasmic reticulum stress, heat shock and arsenic stress. Many mRNA species involved in cell survival and proliferation are more dynamically redistributed, suggesting that mRNA sequestration can be a specific response mechanism through which cells can reshape the landscape of their transcriptome and affect the cell fate determination in stress conditions .
2018-01-01 | GSE90869 | GEO