Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA175434 | ENA |
REPOSITORIES: ENA
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Project description:Quaking is a global regulator of muscle-specific alternative splicing in vertebrates [differentiation data]
| PRJNA175433 | ENA
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: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.
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
Project description:A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA binding protein Rbm24 is a major regulator of muscle specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protein. We built linear models using 2 different experiments and two conditions (miR222 over expression (n=1) and control siRNA(n=2)) with the linear formula (~condition + experiment).
2016-08-22 | E-GEOD-75981 | biostudies-arrayexpress
Project description:Alternative mRNA splicing provides transcript diversity and has been proposed to contribute to several human diseases. Here, we demonstrate that expression of genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. To determine the metabolic impact of reduced splicing factor expression, we further evaluated the splicing factor, SFRS10, identified as down-regulated in obese human liver and skeletal muscle and in high fat fed rodents. siRNA-mediated reductions in SFRS10 expression induced lipogenesis and lipid accumulation in cultured hepatocytes. Moreover, SFRS10 heterozygous mice have both increased hepatic lipogenic gene expression and hypertriglyceridemia. We also demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10, with reduced SFRS10 levels favoring the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished the lipogenic effects of decreased SFRS10 expression. Together, our results indicate reduced expression of SFRS10 alters LPIN1 splicing and induces lipogenesis, demonstrating that reduced splicing factor expression observed in human tissues may contribute to metabolic phenotypes associated with human obesity. Skeletal muscle samples were obtained from 10 lean control subjects and 7 obese subjects with either IGT or DM2 undergoing elective cholecystectomy. Data for liver samples presented in the same manuscript are available at GEO GSE15653. In this analysis RNA was isolated for cRNA preparation and hybridized to Affymetrix Human Genome U133 Plus 2.0 microarrays.
2011-08-02 | E-GEOD-22435 | biostudies-arrayexpress
Project description:Quaking are RNA binding proteins, which are known to regulate the expression of different genes at the post-transcriptional level. Genetic interference with quaking a (qkia) and quaking c (qkic) leads to major myofibril defects during zebrafish development, without affecting early muscle differentiation. In order to understand how qkia and qkic jointly regulate myofibril formation, we performed a comparative analysis of the transcriptome of qkia/qkic (qkia mutant injected with qkic morpholino) versus control embryos. We show that Quaking activity is required for accumulation of the muscle-specific tropomyosin 3 transcript, tpm3.1. Whereas interference with tmp3.1 function disrupts myofibril formation, reintroducing tpm3.1 transcripts into embryos with reduced Quaking activity can restore structured myofibrils. Thus, we identify tropomyosin as an essential component in the process of myofibril formation and as a relay downstream of the regulator proteins Quaking.
2017-09-17 | GSE71573 | GEO
Project description:Alternative mRNA splicing provides transcript diversity and has been proposed to contribute to several human diseases. Here, we demonstrate that expression of genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. To determine the metabolic impact of reduced splicing factor expression, we further evaluated the splicing factor, SFRS10, identified as down-regulated in obese human liver and skeletal muscle and in high fat fed rodents. siRNA-mediated reductions in SFRS10 expression induced lipogenesis and lipid accumulation in cultured hepatocytes. Moreover, SFRS10 heterozygous mice have both increased hepatic lipogenic gene expression and hypertriglyceridemia. We also demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10, with reduced SFRS10 levels favoring the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished the lipogenic effects of decreased SFRS10 expression. Together, our results indicate reduced expression of SFRS10 alters LPIN1 splicing and induces lipogenesis, demonstrating that reduced splicing factor expression observed in human tissues may contribute to metabolic phenotypes associated with human obesity.
2011-08-03 | GSE22435 | GEO