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Overexpression of DDX42 suppresses the altered RNA splicing associated with the K700E mutated SF3B1 in 293T cells

ABSTRACT: We report the bulk RNA-seq in HEK293T cells transfected with DExD/H ATPase and SF3B1

ORGANISM(S): Homo sapiens

PROVIDER: GSE186486 | GEO | 2022/05/20

REPOSITORIES: GEO

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SF3B1 association with chromatin determines splicing outcomes

Project description:Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. Part of the explanation probably lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicated that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses revealed that SF3B1 is specifically bound to nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC content between exons and introns. Disruption of SF3B1 binding to such nucleosomes affected the splicing of these exons similarly to inhibition of SF3B1 expression. Our findings suggest that the association of SF3B1 with nucleosomes is functionally important for splice site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure. MNase-seq on Input and SF3B1 pull-down, mRNA-seq on control and SF3B1 si-RNA treated cells as well as on TSA (Trichostatin A) treated and untreated cells.

2015-04-22 | E-GEOD-65644 | biostudies-arrayexpress

Overexpression of DDX42 suppresses the altered RNA splicing associated with the K700E mutated SF3B1 in 293T cells

Project description:Overexpression of DDX42 suppresses the altered RNA splicing associated with the K700E mutated SF3B1 in 293T cells

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Functional and conformational impact of cancer-associated SF3B1 mutations depends on the position and the charge of amino acid substitution

Project description:RNA-sequencing data from HEK293T cell models: Hek293T transfected with expression vectors of SF3B1-WT, SF3B1-R625H, SF3B1-K666T, SF3B1-K700E.

2021-02-18 | GSE167001 | GEO

Mis-splicing of mitotic regulators sensitizes SF3B1-mutated human HSCs to CHK1 inhibition [scRNA-seq]

Project description:Splicing factor SF3B1 mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences of SF3B1 mutations in human HSCs remain unclear. Here, we identify the mis-splicing program in human HSCs as a targetable vulnerability by precise gene editing of SF3B1 K700E mutations in primary CD34+ cells. Mutant SF3B1 induced pervasive mis-splicing and reduced expression of genes regulating mitosis in single cell transcriptomics, critically BUBR1 and CDC27, leading to altered differentiation and delayed G2/M progression. Mutant SF3B1 mis-splicing or reduced expression of BUBR1 and CDC27 was sufficient to delay G2/M transit, leading to activation of CHK1, sensitizing cells to CHK1 inhibition. Clinical CHK1 inhibitor prexasertib selectively targeted SF3B1-mutant HSCs and abrogated engraftment in vivo. These findings identify mis-splicing of mitotic regulators in SF3B1-mutant HSCs as a targetable vulnerability engaged by pharmacological CHK1 inhibition.

2024-05-29 | GSE263300 | GEO

Mis-splicing of mitotic regulators sensitizes SF3B1-mutated human HSCs to CHK1 inhibition [RNA-seq]

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Genetic alterations of SUGP1 mimic mutant-SF3B1 splice pattern in lung adenocarcinoma and other cancers

Project description:RNA-sequencing data from HEK293T and HAP1 cell models: Hek293T (SF3B1-K700E, SF3B1-WT, SUGP1-KD and siContol), HAP1 CRISPR-isogenic cell lines WT and SUGP1-P636L

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K562 SF3B1 Mutants and Splicing

Project description:This project containins data for K562 cell line experiments with SF3B1 Mutations

2024-11-20 | PXD030127 | Pride

SF3B1 association with chromatin determines splicing outcomes

2015-04-22 | GSE65644 | GEO

Splicing patterns in SF3B1 mutated uveal melanoma generate shared immunogenic tumor-specific neo-epitopes [scRNA-seq]

Project description:Purpose: In this study, we show that mutations of the splicing factor SF3B1 in uveal melanoma (UM) generate immunogenic neo-antigens.

2021-03-26 | GSE169609 | GEO

Splicing patterns in SF3B1 mutated uveal melanoma generate shared immunogenic tumor-specific neo-epitopes [scADT-seq]

Project description:Purpose: In this study, we show that mutations of the splicing factor SF3B1 in uveal melanoma (UM) generate immunogenic neo-antigens.

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