Cell-type specific translational changes in prion diseases
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ABSTRACT:
PROVIDER: PRJNA630198 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11684300.fastq.gz | Fastqsanger.gz | |||
| SRR11684400.fastq.gz | Fastqsanger.gz | |||
| SRR11684301.fastq.gz | Fastqsanger.gz | |||
| SRR11684401.fastq.gz | Fastqsanger.gz | |||
| SRR11684302.fastq.gz | Fastqsanger.gz |
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Project description:Identification of genome-wide translational changes during prion disease via cell-type specific ribosome profiling.
2020-09-29 | GSE149805 | GEO
Project description:Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease.
2023-01-31 | GSE214374 | GEO
Project description:Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease.
2023-01-31 | GSE214373 | GEO
Project description:Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease.
2023-01-31 | GSE214375 | GEO
Project description:Selective vulnerability is an enigmatic feature of neurodegenerative diseases (NDs), whereby a widely expressed protein causes lesions in specific cell types and brain regions. Using the RiboTag method in mice, translational responses of five neural subtypes to acquired prion disease (PrD) were measured. Pre-onset and disease onset timepoints were chosen based on longitudinal electroencephalography (EEG) that revealed a gradual increase in theta power between 10- and 18-weeks after prion injection, resembling a clinical feature of human PrD. At disease onset, marked by significantly increased theta power and histopathological lesions, mice had pronounced translatome changes in all five cell types despite appearing normal. Remarkably, at a pre-onset stage, prior to EEG and neuropathological changes, we found that 1) translatomes of astrocytes indicated reduced synthesis of ribosomal and mitochondrial components, 2) glutamatergic neurons showed increased expression of cytoskeletal genes, and 3) GABAergic neurons revealed reduced expression of circadian rhythm genes. These data demonstrate that early translatome responses to neurodegeneration emerge prior to conventional markers of disease and are cell type-specific. Therapeutic strategies may need to target multiple pathways in specific populations of cells, early in disease.
2022-06-13 | GSE189527 | GEO
Project description:Cytoplasmic RNA granules have emerged as important elements of posttranscriptional and translational regulation. Stress, germinal and neuronal granules contain RNA-binding proteins capable of self-assembly due to prion-like domains. Hyperassembly mediated by these prion-like domains causes several neurodegenerative diseases. Here, we report a subset of the mammalian prion protein (PrP), also prone to self-assembly, propagation and to cause devastating diseases, is a component of naturally occurring messenger ribonucleoproteins (mRNPs) in adult mouse brains. Biomolecules co-purified with PrP revealed a multitude of diverse RNA granule associated proteins and mRNAs encoding members of the translation machinery, indicating a role in a specialized translation process. Importantly, PrP mutations linked to Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI) severely impaired recovery of mRNPs from preclinical mice, possibly representing a very early pathological process. Thus, mutant PrP may cause dysfunction in RNA regulation, thereby joining the constantly expanding ranks of disease associated RNP granule proteins. The file Enrichment_analysis.xlsx contains mRNAs (FDR < 0.01) co-purified with PrP in both WT sample pools as identified by DESeq2 and the respective gene counts and log2 fold changes for CJD and FFI PrP:IP sample pools.
2015-11-01 | GSE57233 | GEO
Project description:Prion diseases are fatal transmissible neurodegenerative conditions of humans and animals that arise through neurotoxicity induced by PrP misfolding. The cellular and molecular mechanisms of prion-induced neurotoxicity remain undefined. Understanding these processes will underpin therapeutic and control strategies for human and animal prion diseases, respectively. Prion diseases are difficult to study in their natural hosts and require the use of tractable animal models. Here we used RNA-Seq-based transcriptome analysis of prion-exposed Drosophila to probe the mechanism of prion-induced neurotoxicity. Adult Drosophila transgenic for pan neuronal expression of ovine PrP targeted to the plasma membrane exhibit a neurotoxic phenotype evidenced by decreased locomotor activity after exposure to ovine prions at the larval stage. Pathway analysis and quantitative PCR of genes differentially expressed in prion-infected Drosophila revealed up-regulation of cell cycle activity and DNA damage response, followed by down-regulation of eIF2 and mTOR signalling. Mitochondrial dysfunction was identified as the principal toxicity pathway in prion-exposed PrP transgenic Drosophila. The transcriptomic changes we observed were specific to PrP targeted to the plasma membrane since these prion-induced gene expression changes were not evident in similarly-treated Drosophila transgenic for cytosolic pan neuronal PrP expression, or in non-transgenic control flies. Collectively, our data indicate that aberrant cell cycle activity, repression of protein synthesis and altered mitochondrial function are key events involved in prion-induced neurotoxicity, and correlate with those identified in mammalian hosts undergoing prion disease. These studies highlight the use of PrP transgenic Drosophila as a genetically well-defined tractable host to study mammalian prion biology.
2020-01-31 | GSE144028 | GEO
Project description:Cytoplasmic RNA granules have emerged as important elements of posttranscriptional and translational regulation. Stress, germinal and neuronal granules contain RNA-binding proteins capable of self-assembly due to prion-like domains. Hyperassembly mediated by these prion-like domains causes several neurodegenerative diseases. Here, we report a subset of the mammalian prion protein (PrP), also prone to self-assembly, propagation and to cause devastating diseases, is a component of naturally occurring messenger ribonucleoproteins (mRNPs) in adult mouse brains. Biomolecules co-purified with PrP revealed a multitude of diverse RNA granule associated proteins and mRNAs encoding members of the translation machinery, indicating a role in a specialized translation process. Importantly, PrP mutations linked to Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI) severely impaired recovery of mRNPs from preclinical mice, possibly representing a very early pathological process. Thus, mutant PrP may cause dysfunction in RNA regulation, thereby joining the constantly expanding ranks of disease associated RNP granule proteins. The file Enrichment_analysis.xlsx contains mRNAs (FDR < 0.01) co-purified with PrP in both WT sample pools as identified by DESeq2 and the respective gene counts and log2 fold changes for CJD and FFI PrP:IP sample pools. RIP-Seq analysis of mRNAs co-purified with PrP from murine brain cytoplasmic fractions in wild-type (WT), CJD and FFI mice. Each RIP-Seq and control (input) library represents a pool of 12 to 16 co-immunoprecipitation samples out of 3 to 4 mice. To control for post-homogenization artifacts, we conducted an experiment in which we prepared homogenates from WT and PrP-KO (Prnp-/-) mice of different genetic backgrounds (C57BL/6 and 129S4) and identified SNPs in RIP-Seq and control libraries to finally identify specifically co-purified mRNAs.
2015-11-01 | E-GEOD-57233 | biostudies-arrayexpress
Project description:Prions are infectious proteins that can adopt a structural conformation different from that of the normal protein. This change of conformation is then propagated among other molecules of the same protein. Prions are associated with neurodegenerative diseases in mammals, but are also found in fungi (in the yeast Saccharomyces cerevisiae and the filamentous fungus Podospora anserina), in which they control heritable traits. They are widespread in wild yeast strains, suggesting a biologically important role. [PSI+] is one of the most widely studied yeast prions. It corresponds to an aggregated conformation of the translational release factor, eRF3, which suppresses nonsense codons. [PSI+] modifies cellular fitness, inducing various phenotypes, depending on the genetic background. However, the genes displaying [PSI+]-controlled expression remain largely unknown. We used the recently described ribosome profiling approach to identify genes displaying changes in expression in the presence of [PSI+]. This made it possible to determine the positions of all active ribosomes within the genome, in both [PSI+] and [PSI-] isogenic strains. Comparisons of the translatomes and transcriptomes of the two strains revealed that the primary effect of [PSI+] was to repress genes involved in the stress response. Thus, we provide the first description of the global translational effect of [PSI+] and a new genetic explanation of the phenotypic differences between [PSI-] and [PSI+] strains under stress conditions. Comparisons of the translatomes and transcriptomes of the two strains. Comparisons of the translatomes of the two strainsM-BM- : a [PSI+] strain (two replicates) and a [PSI+] overexpressing SUP35-Cter strain.
2014-07-18 | E-GEOD-41590 | biostudies-arrayexpress
Project description:We provide here a comprehensive transcriptional profiling of murine blood, spleen and skeletal muscle and brain on eight different time points after intracerebral prion inoculation. Our findings provide a detailed time course of extra-neural, transcriptional changes during prion disease which we presume to be of immediate relevance for biomarker development. Data analysis scripts can be found on https://github.com/marusakod/RML_extraneural_organs.
2022-09-01 | GSE210128 | GEO