Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: MSV000080878PXD001249
PROVIDER: PRJNA260186 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1567910.fastq.gz | Fastqsanger.gz | |||
| SRR1567911.fastq.gz | Fastqsanger.gz | |||
| SRR1567912.fastq.gz | Fastqsanger.gz | |||
| SRR1567905.fastq.gz | Fastqsanger.gz | |||
| SRR1567905_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. SNW1 depletion causes cohesion defects predominantly by reducing sororin levels, which causes destabilisation of cohesin on DNA. SNW1 depletion also reduces APC/C activity and contributes to cohesion defects indirectly by delaying mitosis and causing ‘cohesion fatigue’. Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1 depleted cells. These results indicate that the spliceosome is required for mitosis because it enables expression of genes essential for cohesion. Our transcriptome-wide identification of retained introns in SNW1 and PRPF8 depleted cells may help to understand the aetiology of diseases associated with splicing defects, such as retinosa pigmentosum and cancer.
2016-06-29 | PXD001249 | Pride
Project description:Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. SNW1 depletion causes cohesion defects predominantly by reducing sororin levels, which causes destabilisation of cohesin on DNA. SNW1 depletion also reduces APC/C activity and contributes to cohesion defects indirectly by delaying mitosis and causing ‘cohesion fatigue’. Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1 depleted cells. These results indicate that the spliceosome is required for mitosis because it enables expression of genes essential for cohesion. Our transcriptome-wide identification of retained introns in SNW1 and PRPF8 depleted cells may help to understand the aetiology of diseases associated with splicing defects, such as retinosa pigmentosum and cancer.
2017-04-02 | MSV000080878 | MassIVE
Project description:Transcriptome wide identification of retained introns upon depletion of the splicing factors WBP11 or SNW1
| PRJNA530564 | ENA
Project description:Background: Substantial progress has been made in the identification of sequence elements that control mRNA splicing and the genetic variants in these elements that alter mRNA splicing (referred to as splicing quantitative trait loci -- sQTLs). Genetic variants that affect mRNA splicing in trans are harder to identify because their effects can be more subtle and diffuse, and the variants are not co-located with their targets. We carried out a transcriptome-wide analysis of the effects of a mutation in a ubiquitous splicing factor that causes retinitis pigmentosa (RP) on mRNA splicing, using exon microarrays. Results: Exon microarray data was generated from whole blood samples obtained from four individuals with a mutation in the splicing factor PRPF8 and four sibling controls. Although the mutation has no known phenotype in blood, there was evidence of widespread differences in splicing between cases and controls (affecting between 10\% and 25\% of exons). Most probesets with significantly different inclusion (defined as the expression intensity of the exon divided by the expression of the corresponding transcript) between cases and controls had higher inclusion in cases and corresponded to exons that were shorter than average, AT-rich, located towards the 5' end of the gene and flanked by long introns. Introns flanking affected probesets were particularly depleted for the shortest category of introns, associated with splicing via intron definition. Conclusions: Our results show that a mutation in a splicing factor, with a phenotype that is restricted to retinal tissue, acts as a trans-sQTL cluster in whole blood samples. Characteristics of the affected exons suggest that they are spliced co-transcriptionally and via exon definition. Eight samples consisting of four sibling pairs were analysed. One individual in each pair harboured an RP-causing mutation on the PRPF8 gene (cases). Unaffected siblings were used as controls.
2012-12-25 | E-GEOD-43134 | biostudies-arrayexpress
Project description:While intron retention (IR) is now recognized as a widespread and conserved mechanism of gene expression control, its regulation is poorly understood. Here, we identify significantly reduced DNA methylation levels near splice junctions flanking retained introns compared to non-retained introns in diverse primary cells and cell lines. Further, we identify increased IR following inhibition of DNA methylation indicating that reduced DNA methylation promotes IR. We demonstrate reduced occupancy of MeCP2 near the splice junctions of retained introns, mirroring the reduced DNA methylation at these sites. Accordingly, MeCP2 depletion in tissues/cells enhances IR. By analyzing the MeCP2 interactome, we demonstrate that decreased MeCP2 binding near splice junctions facilitates IR via reduced recruitment of the splicing factor, Tra2b, and increased RNA polymerase II stalling. Our study identifies a dynamic interplay between DNA methylation, MeCP2 and splicing factors including Tra2b in IR regulation and provides novel insights into the mechanisms governing splicing.
2017-02-28 | GSE85517 | GEO
Project description:Dead-box RNA helicases are crucial in mRNA processing, specifically in RNA splicing. Our previous work has shown that DDX39B is responsible for regulating the splicing of IL7R exon 6 and several FOXP3 introns, which rely on DDX39B's helicase and ATPase activities, respectively [this is not accurate since exon 6 also must require the ATPase activity, which is required for helicase activity]. In this study, we aimed to investigate whether DDX39A, a highly homologous paralog of DDX39B, plays a similar role in regulating alternative RNA splicing. We find that DDX39A and DDX39B have significant redundancy in their gene targets, however, DDX39A is incapable of complementing defective splicing of IL7R exon 6 when DDX39B is knockdown. Conversely, overexpressing DDX39A can rescue FOXP3 intron 11 splicing under DDX39B-depleted conditions. In this work we also confirm that introns containing C-rich/U-poor polypyrimidine tract are very sensitive to DDX39B levels. We also observed that cassette exons with C-rich/U-poor py tracts in upstream introns were also sensitive to DDX39B levels and were skipped more upon depletion of DDX39B, but not DDX39A. Among the introns retained more upon DDX39A and DDX39B depletion were DDX39A and DDX39B intron 6, which depend on DDX39A and DDX39B levels, respectively. Therefore, we identified an autoregulatory mechanism through which DDX39A and DDX39B control their respective expression. This study presents evidence that while DDX39A and DDX39B differentially impact certain RNA splicing events, they have many shared targets.
2024-05-29 | GSE253261 | GEO
Project description:Pre-mRNA splicing is a complex and dynamic process that relies on the intricate coordination between a multitude of cis-elements and trans-acting factors. Here, we identify and characterize Silencing Defective 2 (SDE2) as a human RNA binding protein and trans-acting splicing-associated factor required for efficient mRNA processing. In this study, we use Poly(A) purified RNA sequencing to identify the alternative splicing profile in Hela cells following depletion of SDE2 via siRNA. Our data demonstrate that SDE2 depletion causes widespread changes in alternative splicing (AS), with increased intron retention being the most common event. These retained introns are significantly shorter, have a higher GC content, and overall maintain weaker 5' and 3' splice sites than other introns throughout the genome. Following the depletion of SDE2, increased intron retention causes catastrophic consequences for the cell, including defects in mitotic progression, global loss of protein translation, and ultimately, complete loss of cellular viability. Taken together, we define SDE2 as a previously uncharacterized RNA binding protein that functions to regulate pre-mRNA splicing and ensure cellular viability.
2021-01-01 | GSE143258 | GEO
Project description:To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. 87% of introns assayed manifest more than 50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly, or slowly, with ~3% being almost completely retained in nascent pre-mRNA. Although individual introns showed slight but statistically significant differences in splicing efficiency, similar global levels of splicing were seen from both sources. Importantly, introns with low cotranscriptional splicing efficiencies are present in the same primary transcript with efficiently spliced introns, indicating that splicing is intron-specific. The analysis also indicates that cotranscriptional splicing is less efficient for first introns, longer introns and introns annotated as alternative. FinallyFinally, S2 cells expressing the slow RpII215C4 mutant manifest substantially less intron retention than wild-type S2 cells. Examination of Total pA and Nascent RNA from 2 different cell populations and isolated fly heads.
2011-12-01 | E-GEOD-32950 | biostudies-arrayexpress
Project description:Background: Substantial progress has been made in the identification of sequence elements that control mRNA splicing and the genetic variants in these elements that alter mRNA splicing (referred to as splicing quantitative trait loci -- sQTLs). Genetic variants that affect mRNA splicing in trans are harder to identify because their effects can be more subtle and diffuse, and the variants are not co-located with their targets. We carried out a transcriptome-wide analysis of the effects of a mutation in a ubiquitous splicing factor that causes retinitis pigmentosa (RP) on mRNA splicing, using exon microarrays. Results: Exon microarray data was generated from whole blood samples obtained from four individuals with a mutation in the splicing factor PRPF8 and four sibling controls. Although the mutation has no known phenotype in blood, there was evidence of widespread differences in splicing between cases and controls (affecting between 10\% and 25\% of exons). Most probesets with significantly different inclusion (defined as the expression intensity of the exon divided by the expression of the corresponding transcript) between cases and controls had higher inclusion in cases and corresponded to exons that were shorter than average, AT-rich, located towards the 5' end of the gene and flanked by long introns. Introns flanking affected probesets were particularly depleted for the shortest category of introns, associated with splicing via intron definition. Conclusions: Our results show that a mutation in a splicing factor, with a phenotype that is restricted to retinal tissue, acts as a trans-sQTL cluster in whole blood samples. Characteristics of the affected exons suggest that they are spliced co-transcriptionally and via exon definition.
2012-12-25 | GSE43134 | GEO
Project description:In eukaryotic cells, most introns are degraded soon after splicing in the nucleus but some persist either due to lack of splicing (detained/retained introns) or because they contain important functional elements, for example, sno/scaRNAs. Few introns are detectable outside the nucleus. To hunt for interesting new phenomena in cytoplasmic introns and splicing, we conducted a multimodal study of total RNA within projections (axons, dendrites, glial projections) of rat hippocampal neurons and discovered a class of free circular introns enriched in distal projections.
2019-04-18 | GSE129924 | GEO