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SRP018547
Saccharomyces cerevisiae
47 Downloadable Samples
Illumina HiSeq 2000
Description
During meiosis in yeast, global splicing efficiency increases. The mechanism for this is relief of competition for the splicing machinery by repression of intron-containing ribosomal protein genes (RPGs). Repression of RPGs with rapamycin also increases splicing efficiency in vegetative cells. Reducing levels of an RPG-dedicated transcription factor globally improves splicing and suppresses the temperature-sensitive growth defect of a spliceosome mutation. These results indicate that the spliceosome is limiting and pre-mRNAs compete with each other. Under these conditions, splicing efficiency of a given pre-mRNA therefore depends on both its concentration and affinity for the limiting splicing factor(s) as well as those of the competing pre-mRNAs. We propose that trans-competition control of splicing helps repress meiotic gene expression in vegetative cells, and promotes efficient meiosis. Competition between RNAs for a limiting factor may be a general condition important for function of a variety of post-transcriptional control mechanisms. Overall design: Splicing and gene expression profiles of 1) wild type yeast cells treated with rapamycin (2 biological replicates) relative to untreated cells and 2) prp4-1 pGAL-IFH1 (down-regulated expression of IFH1 transcription factor(specific for ribosomal protein genes)) relative to prp4-1 yeast.
Publication Title
Competition between pre-mRNAs for the splicing machinery drives global regulation of splicing.
Sample Metadata Fields
Treatment, Subject
View Samples- Drosophila melanogaster
- 43 Downloadable Samples
- Illumina Genome Analyzer
Description
Comapare the global expression of metafemales and normal femalems Overall design: Collected the metafemales, females and males and made RNA-seq
Publication Title
Dosage compensation and inverse effects in triple X metafemales of Drosophila.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
RNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing Overall design: 12 samples: 3 cell lines (HeLa, HeLa-p150KO, HeLa-ADAR1KO) with four conditions each (no treatment, MeV-vac2(GFP)-infected, MeV-CKO(GFP)-infected, IFNA/D-treated). One biological replicate per sample. In addition, raw data files of 9 samples from series GSE57353 and GSE99392 were re-analyzed using the same data processing pipeline.
Publication Title
Extensive editing of cellular and viral double-stranded RNA structures accounts for innate immunity suppression and the proviral activity of ADAR1p150.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina Genome Analyzer II
Description
Cross-linking and immunoprecipitation coupled with high-throughput sequencing was used to identify binding sites within 6,304 genes as the brain RNA targets for TDP-43, an RNA binding protein which when mutated causes Amyotrophic Lateral Sclerosis (ALS). Use of massively parallel sequencing and splicing-sensitive junction arrays revealed that levels of 601 mRNAs are changed (including Fus/Tls, progranulin, and other transcripts encoding neurodegenerative disease-associated proteins) and 965 altered splicing events are detected (including in sortilin, the receptor for progranulin), following depletion of TDP-43 from adult brain with antisense oligonucleotides. RNAs whose levels are most depleted by reduction in TDP-43 are derived from genes with very long introns and which encode proteins involved in synaptic activity. Lastly, TDP-43 was found to auto-regulate its synthesis, in part by directly binding and enhancing splicing of an intron within the 3’ untranslated region of its own transcript, thereby triggering nonsense mediated RNA degradation. Overall design: RNAseq in control and Tdp-43 knockdown mouse striatum
Publication Title
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
Cross-linking and immunoprecipitation coupled with high-throughput sequencing was used to identify binding sites within 6,304 genes as the brain RNA targets for TDP-43, an RNA binding protein which when mutated causes Amyotrophic Lateral Sclerosis (ALS). Use of massively parallel sequencing and splicing-sensitive junction arrays revealed that levels of 601 mRNAs are changed (including Fus/Tls, progranulin, and other transcripts encoding neurodegenerative disease-associated proteins) and 965 altered splicing events are detected (including in sortilin, the receptor for progranulin), following depletion of TDP-43 from adult brain with antisense oligonucleotides. RNAs whose levels are most depleted by reduction in TDP-43 are derived from genes with very long introns and which encode proteins involved in synaptic activity. Lastly, TDP-43 was found to auto-regulate its synthesis, in part by directly binding and enhancing splicing of an intron within the 3’ untranslated region of its own transcript, thereby triggering nonsense mediated RNA degradation. Overall design: CLIP of Tdp-43 in 8 week mouse brain.
Publication Title
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
In this study, we report that HCMV infection results in widespread alternative splicing (AS), shorter 3'-untranslated regions (3'UTRs) and polyA tail lengthening in host genes and CPEB1 depletion reverses infection-related post-transcriptional changes. Overall design: We performed RNA-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated human foreskin fibroblasts (HFFs). We also performed RNA-seq for lentivirus mediated GFP overexpression (OE) and CPEB1 overexpression human foreskin fibroblasts. Lastly, we performed TAIL-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated HFFs.
Publication Title
RNA-binding protein CPEB1 remodels host and viral RNA landscapes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
Description
Many cancers are postulated to harbor developmental hierarchies in which cells display variability in stem-like character, tumor propagating ability, and proliferation. In glioblastoma (GBM), glioma stem cells (GSCs) reside atop such a tumor cellular hierarchy, and are thought to resist current therapies and thus underlie inevitable relapse. Here we show that GSCs can evade RTK inhibition by reversibly regressing to a slow-cycling state reminiscent of quiescent neural stem cells. This process involves up-regulation of numerous histone demethylases, including KDM6A/B, which remodel the chromatin landscape and are selectively essential for drug persister survival. Chromatin remodeling is accompanied by activation of various neurodevelopmental master regulators and Notch signaling, changes which closely parallel critical aspects of neural stem cell biology. Thus our findings illustrate how cancer cells may hijack native developmental programs for deranged proliferation, adaptation, and tolerance in the face of stress. Our studies highlight key roles for chromatin remodeling and developmental plasticity in GBM biology, and suggest strategies for overcoming therapeutic resistance by targeting epigenetic and developmental pathways. Overall design: ChIP-seq for histone modifications and Notch factors in glioblastoma stem cell lines with various drug treatments RNA-seq in glioblastoma stem cell lines with various drug treatments
Publication Title
Adaptive Chromatin Remodeling Drives Glioblastoma Stem Cell Plasticity and Drug Tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
These experiments aim to determine global gene expression patterns in WT vs KPC isolated pancreatic fibroblasts Overall design: WT or KPC mice were isolated from pancreas and RNA-seq was performed
Publication Title
Stromal ETS2 Regulates Chemokine Production and Immune Cell Recruitment during Acinar-to-Ductal Metaplasia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- IlluminaHiSeq2000
Description
TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3’ untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. Overall design: RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents RNA-seq sample(s).
Publication Title
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3’ untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. Overall design: RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents RNA-seq sample(s).
Publication Title
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.
Sample Metadata Fields
No sample metadata fields
View Samples