RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [P7 cortex]
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PROVIDER: PRJNA480860 | ENA |
REPOSITORIES: ENA
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Project description:During mammalian brain development, neural stem cells (NSCs) initially produce only neurons and subsequently shift to glial production, while it is still unknown what regulates this drastic fate change. Here we discovered RNA-binding protein (RBP) of quaking (Qk) is selectively expressed in NSCs and is essential for switching from neurogenesis to gliogenesis. Using CNS-specific KO mice for Qk, we found that gliogenesis, but not neurogenesis, was specifically disrupted in Qk-/- brains. In glial differentiating condition, Qk-/- NSCs failed to enter gliogenesis but caused ectopic neurogenic gene expression. Pathway analysis of Qk-/- NSCs identified endocytosis as the regulatory functional cluster of Qk which has been shown to facilitate extra-cellular signaling receptors replacement and promote NSC differentiation. Mechanistically, Qk regulates endocytosis pathway genes through stabilizing their mRNAs via Qk binding sequences in 3’UTR. These results uncovered the cell fate determination mechanism of NSCs through mRNA regulation.
2020-11-09 | GSE117016 | GEO
Project description:During mammalian brain development, neural stem cells (NSCs) initially produce only neurons and subsequently shift to glial production, while it is still unknown what regulates this drastic fate change. Here we discovered RNA-binding protein (RBP) of quaking (Qk) is selectively expressed in NSCs and is essential for switching from neurogenesis to gliogenesis. Using CNS-specific KO mice for Qk, we found that gliogenesis, but not neurogenesis, was specifically disrupted in Qk-/- brains. In glial differentiating condition, Qk-/- NSCs failed to enter gliogenesis but caused ectopic neurogenic gene expression. Pathway analysis of Qk-/- NSCs identified endocytosis as the regulatory functional cluster of Qk which has been shown to facilitate extra-cellular signaling receptors replacement and promote NSC differentiation. Mechanistically, Qk regulates endocytosis pathway genes through stabilizing their mRNAs via Qk binding sequences in 3’UTR. These results uncovered the cell fate determination mechanism of NSCs through mRNA regulation.
2020-11-09 | GSE117017 | GEO
Project description:RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development
| PRJNA480859 | ENA
Project description:RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [Dif_NSCs]
| PRJNA480861 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-09 | GSE117018 | 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 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:MicroRNAs have emerged as major genetic elements in the genesis and suppression of cancer. Here, multi-dimensional cancer genome analysis and validation has defined a novel Glioblastoma Multiforme (GBM) tumor suppressor pathway and mechanism of action centered on Quaking (QK), a member of the STAR family of RNA-binding proteins. Combined functional, biochemical and computational studies establish that p53 directly regulates QK gene expression, QK protein binds and stabilizes miR-20a of the cancer-relevant miR-17-92 cluster, and miR-20a in turn functions to regulate TGFβR2 and the TGFβ signaling network. Linkage of these pathway components is supported by their genome and expression status across GBM specimens and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QK-miR-20a axis expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs. This SuperSeries is composed of the SubSeries listed below.
2009-12-30 | GSE19693 | 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 | 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