The Effect of RBM5 Gene Manipulation on Expression Data from Day In Vitro 6 Primary Rat Cortical Neurons
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE98858 | GEO | 2018/02/16
REPOSITORIES: GEO
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Project description:This study analyzed the effect of RBM5 gene deletion in cortical brain tissue on differential gene expression/splicing changes 48h after a traumatic brain injury (TBI). TBI was induced in WT vs. KO mice by controlled cortical impact (CCI) injury. The four grouops included: (1) Sham-WT, (2) CCI-WT, (3) Sham-KO, and (4) CCI-KO. The objective of this study was to test if RBM5 KO decreased the expression of cell death mediators in the contused brain 48h post-injury.
2021-05-12 | GSE128543 | GEO
Project description:RBM5, a regulator of alternative splicing of apoptotic genes, and its close homologues, RBM6 and RBM10, are RNA binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which is frequently altered in lung cancer, can regulate colony and xenograft tumor formation and its modulation recapitulates or antagonizes the effects of RBM5, 6 and 10 in cell colony formation. RBM10 mutations identified in lung cancer cells disrupt NUMB splicing regulation to promote cell growth. Our results reveal a key genetic circuit in the control of cancer cell proliferation. RNA from 3 biological replicates of knockdowns of RBM5, 6 and 10 and a control set were used. Changes between the control and knockdowns were measured based on using a splice-junction array (Affymetrix HJAY).
2013-12-20 | E-GEOD-47431 | biostudies-arrayexpress
Project description:RNA-binding proteins (RBPs) are key players regulating RNA processing and are associated with disorders ranging from cancer to neurodegeneration. Here, we present a proteomics workflow for large-scale identification of RBPs and their RNA-binding regions in the mammalian brain identifying 526 RBPs including 86 previously undescribed. Analysing brain tissue from the Huntington’s disease (HD) R6/2 mouse model uncovered differential RNA-binding of the alternative splicing regulator RBM5. Combining several omics workflows, we show that RBM5 binds differentially to transcripts enriched in pathways of neurodegeneration in R6/2 brain tissue. We further find these transcripts to undergo changes in splicing and demonstrate that RBM5 directly regulates these changes in human neurons derived from embryonic stem cells. Finally, we reveal that RBM5 interacts differently with several known huntingtin interactors and components of huntingtin aggregates. Collectively, we demonstrate the applicability of our method for capturing RNA interactor dynamics in the contexts of tissue and disease.
2023-06-22 | PXD029227 | Pride
Project description:RBM5 and RBM10 are RNA-binding proteins and splicing regulators. These two proteins are putative paralogs in mammalian cells, sharing common domain organization and extensive protein sequence similarity, but their RNA-binding preferences differ. We developed a sensitive system to identify splicing events regulated by RBM5 and/or RBM10, deleting all RBM5 alleles in 293Flp-In cells, and reducing the expression of RBM10, which is partially rescued by activation of a cryptic exon (CE) in one of the RBM10 alleles. RBM5 or RBM10 transgenes were then introduced in these RBM5-null, RBM10 mutant cells (RBM5-/-;RBM10-/CE), allowing controlled protein expression, induced with Doxycycline. Using this system we identify thousands of RBM5 and RBM10-regulated cassette exons, and note a substantial overlap between the two sets.
2024-03-08 | GSE240259 | GEO
Project description:RBM5, a regulator of alternative splicing of apoptotic genes, and its close homologues, RBM6 and RBM10, are RNA binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which is frequently altered in lung cancer, can regulate colony and xenograft tumor formation and its modulation recapitulates or antagonizes the effects of RBM5, 6 and 10 in cell colony formation. RBM10 mutations identified in lung cancer cells disrupt NUMB splicing regulation to promote cell growth. Our results reveal a key genetic circuit in the control of cancer cell proliferation. CLIP-Seq analysis of RBM5, RBM6 and RBM10, with 2 biological replicates and one non-specific control for each protein.
2013-12-20 | E-GEOD-48066 | biostudies-arrayexpress
Project description:RBM5, a regulator of alternative splicing of apoptotic genes, and its close homologues, RBM6 and RBM10, are RNA binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which is frequently altered in lung cancer, can regulate colony and xenograft tumor formation and its modulation recapitulates or antagonizes the effects of RBM5, 6 and 10 in cell colony formation. RBM10 mutations identified in lung cancer cells disrupt NUMB splicing regulation to promote cell growth. Our results reveal a key genetic circuit in the control of cancer cell proliferation.
2013-12-20 | GSE47431 | GEO
Project description:RBM5, a regulator of alternative splicing of apoptotic genes, and its close homologues, RBM6 and RBM10, are RNA binding proteins frequently deleted or mutated in lung cancer. We report that RBM5/6 and RBM10 antagonistically regulate the proliferative capacity of cancer cells and display distinct positional effects in alternative splicing regulation. We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation. NUMB alternative splicing, which is frequently altered in lung cancer, can regulate colony and xenograft tumor formation and its modulation recapitulates or antagonizes the effects of RBM5, 6 and 10 in cell colony formation. RBM10 mutations identified in lung cancer cells disrupt NUMB splicing regulation to promote cell growth. Our results reveal a key genetic circuit in the control of cancer cell proliferation.
2013-12-20 | GSE48066 | GEO
Project description:Background: The oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated. Results: Here, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription. Conclusions: We identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment. Keywords: Acute myeloid leukemia; CRISPR screen; Genome editing; HOXA9; RBM5.
2023-11-16 | GSE225633 | GEO
Project description:We isolated snRNP complexes derived from precatalytic A or B-like spliceosomes solubilized from the chromatin pellet of lysed nuclei. These complexes contained U2 snRNP proteins and a portion of the U2 snRNA, bound with intronic branch sites prior to the first catalytic step of splicing. The complexes have similar composition, whether directly isolated from extracted material, or after selection from glycerol gradients. Here we describe sequencing libraries prepared from RNA derived from directly isolated (IP-seq), or gradient-purified complexes (RNP-seq). Libraries from deproteinized RNA were prepared after selective degradation of U2 snRNA, each in a triplicate. An additional library from RBM5-Flag RNP complex was prepared without such degradation. The majority of sequenced pre-mRNA fragments map to intronic branch sites.
2024-03-08 | GSE240596 | GEO
Project description:Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology. 9 experiments, gene expression measured by Affymetrix microarray. 1) cultured mouse cortical neurons treated with 300nM topotecan vs vehicle-treated controls 2) cultured mouse neurons treated with 1uM topotecan vs vehicle-treated controls 3) cultured mouse cortical neurons treated with 3uM ICRF-193 vs vehicle-treated controls. 4) cultured mouse cortical neurons treated with 10 uM irinotecan vs vehicle-treated controls. 5) cultured mouse cortical neurons treated with 3-1000 nM topotecan vs vehicle treated controls 6) cultured mouse cortical neurons treated with lentivirus expressing shRNA against Top1 and Top2b vs scrambled shRNA controls 7) cultured mouse cortical neurons treated with DRB vs vehicle-treated controls 8) cultured mouse cortical neurons treated with hydrogen peroxide or paraquat vs vehicle-treated controls 9) cultured mouse cortical neurons treated with topotecan with or without subsequent drug washout, vs vehicle-treated controls.
2013-08-30 | E-GEOD-43899 | biostudies-arrayexpress