Mutations mapping to the RNA-binding interface of EXOSC3 have been linked to the rare neurological disorder known as Pontocerebellar Hypoplasia type1B (PCH1B). EXOSC3 is part of three putative RNA-binding structural cap proteinsthat guideRNA intothe RNA exosome, thecellular machinery that2degrades RNA. Here, using RNAcompete, we identifieda G-rich RNA motifthat requirestheK homology and ribosomal protein S1domains of EXOSC3. Interestingly, several PCH1B-causing mutations in EXOSC3do not engage this RNA motif. To test the hypothesis thatmodificationof the RNA-protein interface in EXOSC3 mutants may be phenocopied by small molecules, we performedan in silicoscreen of 50,000 small molecules and used enzyme-linked immunosorbant assays(ELISAs)to assess the ability ofthe molecules to inhibit RNA-bindingbyEXOSC3. We identified asmall molecule, EXOSC3-RNA disrupting (ERD) compound 3 (ERD03), which: (i) bound specifically to EXOSC3in saturation transfer difference nuclear magnetic resonance (STD NMR); (ii)disruptedthe EXOSC3-RNAinteraction in a concentration-dependent manner; (iii) induced an abnormal curved spine PCH1B-like phenotype in zebrafish embryos.This compound induced a comparable modification of RNA expression levels coupled with an atrophy of the cerebellum in the zebrafish. To our knowledge, this is the first example of a small molecule obtained by rational design thatmodelsthe abnormal developmental effectsof a neurodegenerative diseasein a whole organism.
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Sex, Age, Specimen part, Disease, Treatment
View SamplesTranscripomic analysis of leaf gene expression in S and N-deficient winter wheat during grain development. Tissue was harvested at anthesis and 7, 14 and 21 days post anthesis from experimental field plots.
Co-ordinated expression of amino acid metabolism in response to N and S deficiency during wheat grain filling.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesWild type and transgenic msi1-tap1 plants were grown and gene expression was compared at two time points at the age of 8 days.
Regulation of flowering time by Arabidopsis MSI1.
Age, Time
View SamplesTumor recurrence and metastasis remain unavoidable due to a distinct tumor subpopulation known as cancer stem cells (CSCs). To explore the unique cell types contribute to colorectal cancer (CRC) progression, we profiled 831 single cells by simultaneous analysis of RNA sequencing (scRNA-seq) and telomere length in the same cell. Specific markers CD44, CD133 and LGR5 were used to enrich. We find small subpopulations with special features including quiescent CSCs, and epithelial lineage cancer cells (EPCs). Those quiescent CSCs have distinct features including higher level of pluripotency and Wnt signature, and shorter telomeres. Lineage tracing analysis showed that quiescent CSCs could plasticized and generate to epithelial lineage cancer cells with high proliferation and telomeres elongation, and these cells could also transform to each other. New marker genes for CSCs were identified including PROX1, TNFRSF19 and SMOC2. Survival analysis revealed that higher signatures of CSCs and EPCs predicts poor clinical outcome in CRC patients and could be a prognostic biomarkers. These findings provide insight into molecular classification of colorectal cancers and telomere function in CSCs.
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Sex, Age, Specimen part
View Sampleswe construct a comprehensive mouse transcriptomic BodyMap across 17 tissues of six-weeks old C57BL/6JJcl mice using RNA-seq. We find different expression patterns between protein-coding and non-coding genes. Liver and adrenal gland expressed the least complex transcriptome, whereas testis and ovary harbor more complex transcriptome than other tissues. We report a comprehensive list of tissue-specific genes across 17 tissues. Our study provides a unique resource of mouse gene-expression profiles, which is helpful for further biomedical research.
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Sex, Specimen part, Cell line
View SamplesTo investigate the random X chromosome inactivation in vivo, we used allelic-specific RNA sequencing of single cells in mouse model. The intercross was between two genetically distant strains, C57BL/6 and PWK/Ph.
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Sex, Specimen part, Disease, Disease stage, Cell line
View SamplesTo obtain a comprehensive understanding of transcriptomic reprogramming under salt stress, we performed whole genome RNA sequencing on salt-treatment soybean seedlings, on two tissues in a time-course experiment (0h, 1h, 2h, 4 h, 24h and 48h). This time series dataset enables us to identify important hubs and connection of gene expressions. We highlighted the analysis of phytohormone signaling pathways and their possible cross-talking. Gene expression regulation also controls adjustment of carbon and nitrogen metabolism. In general, the treated seedlings had turned off the photosynthetic mechanism and enhanced sugar catabolism to provide energy for survival. Primary nitrogen assimilation was shut down while re-distribution of nitrogen resources was activated. Genes for other protective mechanisms were also induced, including structural modification, ion-sequestering, and scavenging of reactive oxygen species.
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Specimen part, Disease, Treatment
View SamplesRNA-sequencing was used on leaf tissue from 29 diverse maize lines to characterize differences in gene expression between lines. The main goal from this study was to relate gene expression to measured traits of interest.
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Age, Specimen part
View SamplesIn order to study translational control by cis-regulatory elements in untranslated region of mRNA, ribosome profiling assays during different developmental stages of Drosophila melanogaster and in S2 cells cultured in normal and stressful conditions were performed.
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Sex, Specimen part, Cell line
View SamplesIn this study the generic impact of protein aggregation (aggregation of proteins not associated with neurodegenerative disease) on gene expression in cultured cells was investigated by DNA microarray technology. The survey of gene expression showed that the Hsp40, Hsp70 and Hsp105 genes, all of which have documented aggregation suppression activity, were up-regulated. Unexpectedly, the survey also showed increased expression of the MEK5 gene with concomitant silencing of the MEK3 gene. The expression pattern of MEK5 at the mRNA and protein levels aligns with the kinetics of aggregate formation and dissolution. Cell viability was unaffected by protein aggregates. These findings are of particular importance for chronic neurodegenerative diseases where the intraneuronal accumulation of aggregate-prone proteins are a major characteristic of the diseases. The identification of changes in MEK5 gene expression have been observed in Alzheimer-related diseases which provides new diagnostic and therapeutic avenues in these diseases. The molecular neuropathological findings would not have occurred without the generic microarray analyses.
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Specimen part, Cell line, Time
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