RNA-Seq analysis, transcriptome assembly and gene expression profile analysis for vascular smooth muscle cells with upregulation of RBM10
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE188258 | GEO | 2021/11/07
REPOSITORIES: GEO
Similar Datasets
Project description:To understand the role of Cklf1 in the proliferation of vascular smooth muscle cells (VSMC), we quantified the whole genome transcriptomes of VSMC that were treated by Cklf1 adenovirus (n=3) or control (n=3) for 24 h using RNA-seq. In total, we obtained over 82 million clean reads from each library after trimming adaptor sequences, low quality reads and multiple mapped reads. The clean reads were mapped to 29330 genes annotated in the rat reference genome (Rattus_norvegicus 6.0). We then identified differentially expressed genes (DEGs) between Cklf1-associated adenovirus and controls by comparing RNA-Seq data between the two groups. A total of 238 DEGs for Ad-GFP vs. Ad-Cklf1 and 468 DEGs for shRNA Scramble vs. shRNA Cklf1 were defined using the thresholds of FDR ≤ 0.05, difference ratio of FPKM (fragments per kilobase of exon model per million mapped fragments) ≥ 2 and diverge probability ≥ 0.8. The increased CKLF1 resulted in 34 up-regulated and 204 down-regulated genes while knockdown of Cklf1 led to 358 up-regulated and 110 down-regulated genes.
2021-03-05 | GSE111398 | GEO
Project description:Splicing factors have recently been shown to be involved in heterochromatin formation, but their role in controlling heterochromatin structure and function remains poorly understood. In this study, we identified a fission yeast homologue of human splicing factor RBM10, which has been linked to TARP syndrome. Overexpression of Rbm10 in fission yeast leads to strong global intron retention. Rbm10 also interacts with splicing factors in a pattern resembling that of human RBM10, suggesting that the function of Rbm10 as a splicing regulator is conserved. Surprisingly, our deep-sequencing data showed that deletion of Rbm10 caused only minor effect on genome-wide gene expression and splicing. However, the mutant displays severe heterochromatin defects. Further analyses confirmed that the heterochromatin defects in the mutant did not result from mis-splicing of heterochromatin factors. Our proteomic data revealed that Rbm10 associates with the histone deacetylase Clr6 complex and chromatin remodeling complexes known to be essential for heterochromatin silencing. We propose that Rbm10 serves as a platform to recruit Clr6 and chromatin remodelers to mediate heterochromatin formation. Our work together with previous findings further suggests that different splicing subunits may play distinct roles in heterochromatin regulation.
2017-01-23 | GSE93906 | GEO
Project description:RNA-seq in isogenic RBM10-proficient and RBM10-deficient cells derived from lung adenocarcinoma cell lines HCC827 (parental and RBM10 knockout; control siRNA and RBM10 siRNA) and NCI-H1299 (parental and RBM10 knockout).
2024-04-01 | E-MTAB-13617 | biostudies-arrayexpress
Project description:Genome-wide CRISPR-Cas9 knockout screen using TKOv1 sgRNA library was performed in isogenic RBM10-proficient and RBM10-deficient HCC827 cells.
2023-03-04 | E-MTAB-12724 | biostudies-arrayexpress
Project description:RBM10 is an RNA binding protein that was identified as a component of spliceosome complex, suggesting its potential role in splicing regulation. However, the direct experimental evidence for this function has been lacking. Here we characterized in vivo RBM10-RNA interactions and investigated the role of RBM10 in splicing regulation at the global level. We observed significant RBM10-RNA interactions in the vicinity of splice sites and identified hundreds of splicing changes following perturbation of cellular RBM10 abundance. A RNA splicing map integrating the binding pattern and splicing profiles revealed a significant correlation between RBM10-enhanced exon skipping events and its binding close to the splicing sites of both upstream and downstream introns. Furthermore, we demonstrated the splicing defects in a patient carrying a RBM10 mutation. Overall, our data provided insights into the mechanistic model of RBM10-mediated splicing regulation and established genomic resources for future studies on its function in different pathophysiological contexts. We sequenced the mRNA of HEK293 cells and LCL cells, and we determined the RBM10 binding sites using PARCLIP in HEK293 cells. In total we sequenced four mRNA-Seq libraries for KD and two for OE in HEK293 cells; for each of these libraries, we also sequenced one control library. We also sequenced the mRNA of one patient LCL and two normal LCL libraries. Two replicates of PARCLIP sequencing were perfomed.
2013-09-03 | E-GEOD-44976 | biostudies-arrayexpress
Project description:RBM10 is an RNA binding protein that was identified as a component of spliceosome complex, suggesting its potential role in splicing regulation. However, the direct experimental evidence for this function has been lacking. Here we characterized in vivo RBM10-RNA interactions and investigated the role of RBM10 in splicing regulation at the global level. We observed significant RBM10-RNA interactions in the vicinity of splice sites and identified hundreds of splicing changes following perturbation of cellular RBM10 abundance. A RNA splicing map integrating the binding pattern and splicing profiles revealed a significant correlation between RBM10-enhanced exon skipping events and its binding close to the splicing sites of both upstream and downstream introns. Furthermore, we demonstrated the splicing defects in a patient carrying a RBM10 mutation. Overall, our data provided insights into the mechanistic model of RBM10-mediated splicing regulation and established genomic resources for future studies on its function in different pathophysiological contexts.
2013-09-03 | GSE44976 | GEO
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:Genome-wide CRISPR-Cas9 knockout screen using TKOv1 sgRNA library performed in isogenic RBM10-proficient and RBM10-deficient HCC827 cells.
2024-03-01 | E-MTAB-13626 | biostudies-arrayexpress
Project description:Oncogene-driven lung cancers such as those with activating mutations in the epidermal growth factor receptor (EGFR) often harbor additional co-occurring genetic alterations. The significance of most alterations co-occurring with mutant EGFR remains unclear. We report the impact of loss of the mRNA splicing factor RBM10 in human EGFR mutant lung cancer. RBM10 loss decreased EGFR inhibitor efficacy in patient-derived EGFR mutant tumor models. RBM10 regulated mRNA splicing of the mitochondrial apoptotic regulator Bcl-x. Genetic inactivation of RBM10 diminished EGFR inhibitor-mediated apoptosis by altering Bcl-x splicing, decreasing Bcl-xS (pro-apoptotic) and increasing Bcl-xL (anti-apoptotic) levels. Co-inhibition of Bcl-xL and mutant EGFR overcomes resistance induced by RBM10 loss. RBM10 loss was a biomarker of poor response to EGFR inhibitor treatment in clinical samples. Inactivation of the splicing factor RBM10 is a key co-occurring genetic alteration in EGFR mutant tumors that limits EGFR inhibitor efficacy and a potential biomarker of Bcl-xL inhibitor response.
2022-06-04 | GSE199240 | GEO
Project description:RBM10 is an RNA-binding protein that plays an essential role in development and is frequently mutated in the context of human disease. RBM10 recognizes a diverse set of RNA motifs in introns and exons and regulates alternative splicing. However, the molecular mechanisms underlying this seemingly relaxed sequence specificity are not understood and functional studies have focused on 3’ intronic sites only. Here we dissect the RNA code recognized by RBM10 and relate it to the splicing regulatory function of this protein. We show that a two-domain RRM1-ZnF unit recognises a GGA-centred motif enriched in RBM10 exonic sites with high affinity and specificity and test that the interaction with these exonic sequences promotes exon skipping. Importantly, a second RRM domain (RRM2) of RBM10 recognises a C-rich sequence, which explains its known interaction with the intronic 3’ site of NUMB exon 9 contributing to regulation of the Notch pathway in cancer. Together, these findings explain RBM10’s broad RNA specificity and suggest that RBM10 functions as a splicing regulator using two RNA-binding units with different specificities to promote exon skipping.
2017-08-15 | GSE96990 | GEO