Transcriptome-wide regulation of pre-mRNA splicing and expression by the RNA-binding protein Quaking during monocyte to macrophage differentiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA302113 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2923170_1.fastq.gz | Fastqsanger.gz | |||
| SRR2923170_2.fastq.gz | Fastqsanger.gz | |||
| SRR2923171_1.fastq.gz | Fastqsanger.gz | |||
| SRR2923171_2.fastq.gz | Fastqsanger.gz | |||
| SRR2923172_1.fastq.gz | Fastqsanger.gz |
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Project description:Expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts. RNA-seq analysis of primary monocytes and macrophages from a QKI haploinsufficient patient and their (control) sibling.
2016-01-04 | E-GEOD-74978 | biostudies-arrayexpress
Project description:Expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts. Microarray analysis of gene expression and splicing in THP-1 cells transfected with shRNAs, with or without PMA treatment to induce differentiation. 12 total samples were analyzed: THP-1 monocytic cell line transfected with QKI or control shRNAs; samples taken at day 0 or day 3 of PMA-induced differentiation into macrophages.
2016-01-04 | E-GEOD-74887 | biostudies-arrayexpress
Project description:Expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts. Microarray analysis of gene expression and splicing in THP-1 cells transfected with shRNAs, with or without PMA treatment to induce differentiation.
2016-01-04 | GSE74887 | GEO
Project description:Expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts.
2016-01-04 | GSE74978 | GEO
Project description:This work provides the first evidence that Qk is a global regulator of splicing in vertebrates, defines a new splicing regulatory network in muscle, and suggests that overlapping splicing networks contribute to the complexity of changes in alternative splicing during differentiation. Alternative splicing contributes to muscle development and differentiation, but the complete set of muscle splicing factors and their combinatorial interactions are not known. Previously work identifies ACUAA (STAR motif) as an enriched sequence near muscle-specific alternative exons such as Capzb exon 9. We did mass spectrometry of proteins selected by wild type and mutant Capzb intron 9 RNA affinity chromatography, and identified Quaking (Qk), a protein known to regulate mRNA function through ACUAA motifs in 3' UTRs. We show that in myoblasts, Qk promotes inclusion of Capzb exon 9 in opposition to repression by PTB. Qk knockdown in myoblasts has little effect on transcript levels, but alters inclusion of 824 cassette exons whose adjacent intron sequences are enriched in ACUAA motifs. During differentiation to myotubes, Qk levels increase 2-3 fold, suggesting a mechanism for Qk-responsive exon regulation. We captured the PTB splicing regulatory network and intersected it with the Qk network, identifying overlap between the functions of Qk and PTB. Approximately 60% of exons whose inclusion is altered during myogenesis appear to be under control of one or both of these splicing factors in myoblasts. This series is the C2C12 differentiation data. It is 9 arrays, 3 timepoints, with 3 replicates. The time points are 0 hrs, 24 hrs, and 72hrs.
2013-06-05 | E-GEOD-40956 | biostudies-arrayexpress
Project description:This work provides the first evidence that Qk is a global regulator of splicing in vertebrates, defines a new splicing regulatory network in muscle, and suggests that overlapping splicing networks contribute to the complexity of changes in alternative splicing during differentiation. Alternative splicing contributes to muscle development and differentiation, but the complete set of muscle splicing factors and their combinatorial interactions are not known. Previously work identifies ACUAA (STAR motif) as an enriched sequence near muscle-specific alternative exons such as Capzb exon 9. We did mass spectrometry of proteins selected by wild type and mutant Capzb intron 9 RNA affinity chromatography, and identified Quaking (Qk), a protein known to regulate mRNA function through ACUAA motifs in 3' UTRs. We show that in myoblasts, Qk promotes inclusion of Capzb exon 9 in opposition to repression by PTB. Qk knockdown in myoblasts has little effect on transcript levels, but alters inclusion of 824 cassette exons whose adjacent intron sequences are enriched in ACUAA motifs. During differentiation to myotubes, Qk levels increase 2-3 fold, suggesting a mechanism for Qk-responsive exon regulation. We captured the PTB splicing regulatory network and intersected it with the Qk network, identifying overlap between the functions of Qk and PTB. Approximately 60% of exons whose inclusion is altered during myogenesis appear to be under control of one or both of these splicing factors in myoblasts. This series is the C2C12 Qk and PTB siRNA data. It is 12 arrays: 3 PTB siRNA arrays , 3 Qk siRNA arrays, and 6 mock siRNA arrays.
2013-06-05 | E-GEOD-40961 | biostudies-arrayexpress
Project description:A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.
| S-EPMC4821877 | biostudies-literature
Project description:We used a multi-omics approach combining transcriptomics, proteomics and metabolomics to study the impact of over-expression and inhibition of the microRNA miR-223, a pleiotropic regulator of metabolic-related disease, in the RAW monocyte-macrophage cell line. We analyzed the levels of proteins, mRNAs, and metabolites in order to identify genes involved in miR-223 regulation, to determine candidate disease biomarkers and potential therapeutic targets. We observed that both up- and down-regulation of miR-223 induced profound changes in the mRNA, protein and metabolite profiles in RAW cells. Microarray-based transcriptomics evidenced a change in 120 genes that were linked predominantly to histone acetylation, bone remodeling and RNA regulation. In addition, 30 out the 120 genes encoded long noncoding RNAs. The nanoLC-MS/MS revealed that 52 proteins were significantly altered when comparing scramble, pre- and anti-miR-223 treatments. Sixteen out of the mRNAs coding these proteins genes are predicted to have binding sites for miR-223. CARM-1, Ube2g2, Cactin and Ndufaf4 were confirmed to be miR-223 targets by western blotting. Analyses using Gene Ontology annotations evidenced association with cell death, splicing and stability of mRNAs, bone remodeling and cell metabolism. miR-223 alteration changed the expression of CARM-1, Ube2g2, Cactin and Ndufaf4 during osteoclastogenesis and macrophage, indicating that these genes are potential biomarkers of these processes. The most important discriminant metabolites found in the metabolomics study were found to be hydrophilic amino acids, carboxylic acids linked to metabolism and pyrimidine nucleotides, indicating that changes in miR-223 expression alter the metabolic profile of cells, and may affect their apoptotic and proliferative state.
2021-03-29 | PXD009844 | Pride
Project description:This work provides the first evidence that Qk is a global regulator of splicing in vertebrates, defines a new splicing regulatory network in muscle, and suggests that overlapping splicing networks contribute to the complexity of changes in alternative splicing during differentiation. Alternative splicing contributes to muscle development and differentiation, but the complete set of muscle splicing factors and their combinatorial interactions are not known. Previously work identifies ACUAA (STAR motif) as an enriched sequence near muscle-specific alternative exons such as Capzb exon 9. We did mass spectrometry of proteins selected by wild type and mutant Capzb intron 9 RNA affinity chromatography, and identified Quaking (Qk), a protein known to regulate mRNA function through ACUAA motifs in 3' UTRs. We show that in myoblasts, Qk promotes inclusion of Capzb exon 9 in opposition to repression by PTB. Qk knockdown in myoblasts has little effect on transcript levels, but alters inclusion of 824 cassette exons whose adjacent intron sequences are enriched in ACUAA motifs. During differentiation to myotubes, Qk levels increase 2-3 fold, suggesting a mechanism for Qk-responsive exon regulation. We captured the PTB splicing regulatory network and intersected it with the Qk network, identifying overlap between the functions of Qk and PTB. Approximately 60% of exons whose inclusion is altered during myogenesis appear to be under control of one or both of these splicing factors in myoblasts.
2013-06-05 | GSE40961 | GEO
Project description:This work provides the first evidence that Qk is a global regulator of splicing in vertebrates, defines a new splicing regulatory network in muscle, and suggests that overlapping splicing networks contribute to the complexity of changes in alternative splicing during differentiation. Alternative splicing contributes to muscle development and differentiation, but the complete set of muscle splicing factors and their combinatorial interactions are not known. Previously work identifies ACUAA (STAR motif) as an enriched sequence near muscle-specific alternative exons such as Capzb exon 9. We did mass spectrometry of proteins selected by wild type and mutant Capzb intron 9 RNA affinity chromatography, and identified Quaking (Qk), a protein known to regulate mRNA function through ACUAA motifs in 3' UTRs. We show that in myoblasts, Qk promotes inclusion of Capzb exon 9 in opposition to repression by PTB. Qk knockdown in myoblasts has little effect on transcript levels, but alters inclusion of 824 cassette exons whose adjacent intron sequences are enriched in ACUAA motifs. During differentiation to myotubes, Qk levels increase 2-3 fold, suggesting a mechanism for Qk-responsive exon regulation. We captured the PTB splicing regulatory network and intersected it with the Qk network, identifying overlap between the functions of Qk and PTB. Approximately 60% of exons whose inclusion is altered during myogenesis appear to be under control of one or both of these splicing factors in myoblasts.
2013-06-05 | GSE40956 | GEO