Effect of SRSF2 over-expression in a human lung carcinoma cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE50467 | GEO | 2013/08/30
SECONDARY ACCESSION(S): PRJNA217533
REPOSITORIES: GEO
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Project description:We showed that the over-expression of the SR protein SRSF2 led to the regulation of transcript abundance of many genes. H358 cell line with 6 samples with SRSF2 over-expression and 6 samples as control.
2013-08-30 | E-GEOD-50467 | biostudies-arrayexpress
Project description:We showed that the over-expression of the SR protein SRSF2 led to the regulation of transcript abundance of many genes. H358 cell line with 6 samples with SRSF2 over-expression and 6 samples as control.
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Project description:Immune checkpoints blockade therapy may have clinical symptoms of hyper-progressiveness (HP). The molecular mechanism of HP is still to be revealed. This study inspected transcriptome difference between clinical hyper-progressive samples to immunotherapy-response samples based public datasets. Spliceosome factors SRSF2 were found most enriched in neoantigen-related splicing events. Similar splicing pattern and increased cell invasion were found in two lung cancer cell lines after SRSF2 over-expressed.This study shows that dysregulation of SRSF2 -related splicing might be an important feature of immune hyper-progress occurrence.
2022-10-31 | GSE186872 | GEO
Project description:Mutations within genes encoding spliceosomal proteins are the most common class of mutations in patients with myelodysplastic syndromes, yet it is currently not well understood how these mutations impact hematopoiesis or RNA splicing. Here we report that mutations affecting the splicing factor SRSF2 alter its normal RNA recognition activity, resulting in impaired hematopoietic differentiation and myelodysplasia. Commonly occurring SRSF2 mutations impaired wildtype SRSF2’s normal RNA-binding avidity and preference for specific exonic splicing enhancer RNA motifs. Integration of murine and human transcriptome data identified recurrent mis-splicing of key transcriptional regulators in the presence of mutant SRSF2, including promotion of a highly conserved “poison” exon of EZH2 that results in nonsense-mediated decay and contributes to impaired hematopoiesis. These data provide a mechanistic basis for the enrichment of specific mutations in spliceosomal proteins in myelodysplasia, and suggest that altered RNA recognition activity is a novel mechanism of leukemogenesis. mRNA profiles of murine model and K562 cells expressing SRSF2 WT, mutants and knockdown of SRSF2 in TF-1 cells generated by deep sequencing.
2015-05-12 | E-GEOD-65349 | biostudies-arrayexpress
Project description:Mutations in the splicing factor Serine Arginine Rich Splicing Factor 2 (SRSF2) occur in over 30% of patients with myelodysplasia (MDS) and a subset of patients with acute myeloid leukemia (AML) and portend a poor prognosis. SRSF2 is ubiquitously expressed and directs exon inclusion or exclusion in a sequence and context dependent manner. SRSF2 mutations almost exclusively affect the proline at position 95 in the C-terminus of the RNA binding domain. We here show how a mutation in SRSF2 (P95H) affects its normal function in vivo on a transcriptome-wide basis via RNA crosslinking and immunoprecipitation (HITS-CLIP) and parallel quantification of transcript levels (RNA-seq), leading to the identification of differentially bound and alternatively spliced SRSF2 targets. Keywords: Splicing, myeloid neoplasia, SRSF2, HITS-CLIP
2018-06-18 | GSE111900 | GEO
Project description:Recurrent Glycogen synthase kinase-3 (GSK-3) phosphorylates multiple splicing factors, including SRSF2, and regulates the splicing of a broad range of mRNAs in human cells. Inhibition of GSK-3 disrupts splicing and promotes cell death in hematopoietic cells with heterozygous mutations in SRSF2 and not in cells with wild-type splicing factors. To characterize how GSK-3 inhibition alters the cellular proteome in SRSF2-P95H/+ cells, we have performed quantitative mass spectrometry (qMS) on K562 cells with SRSF2P95H/+ knocked into the endogenous locus (PMID 30799057) and parental K562 cells, treated with the GSK-3 inhibitor CHIR99021. We focused on the mitochondrial proteome using human proteome (UniprotKB) and mitochondrial (MitoCarta 3.0) databases for protein identification, identifying 163 mitochondrial proteins whose levels are affected by SRSF2 mutation.
2024-06-22 | PXD043213 | Pride
Project description:SRSF2 is an RNA binding protein that plays important roles in splicing of mRNA precursors. Mutations in SRSF2 are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how they affect SRSF2 function has only begun to be examined. Here we used CRISPR/Cas9 to introduce the P95H mutation to SRSF2 in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (<1% of total). Of these, 374 involve the inclusion of cassette exons, and the inclusion was either increased (206) or decreased (168). We detected a specific motif (UCCA/UG) enriched in the more included exons and a distinct motif (UGGA/UG) in the more excluded exons. RNA gel shift assays showed that a mutant SRSF2 derivative bound more tightly than its wild-type counterpart to RNA sites containing UCCAG, but less tightly to UGGAG sites. The pattern of exon inclusion or exclusion thus correlated in most cases with stronger or weaker RNA binding, respectively. We further show that the P95H mutation does not affect other functions of SRSF2, i.e., protein-protein interactions with key splicing factors. Our results thus demonstrate that the P95H mutation positively or negatively alters the binding affinity of SRSF2 for cognate RNA sites in target transcripts, leading to misregulation of exon inclusion. Our findings not only shed light on the mechanism of the disease-associated SRSF2 mutation in splicing regulation, but also reveal a group of mis-spliced mRNA isoforms for potential therapeutic targeting. Examination of differentially spliced events in K562 CRISPR cell clones (with wild-type or mutant SRSF2) by RNA sequencing
2015-08-10 | E-GEOD-71299 | biostudies-arrayexpress
Project description:RNA-seq study of SRSF2 over-expressing lung cancer cell lines
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Project description:We report insulin secretion defects in SRSF2 Ins2-Cre mice, in which SRSF2 is ablated in pancreatic β cells.
2024-04-28 | GSE175969 | GEO
Project description:SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. Here, we report global analyses of two prototypical SR proteins SRSF1 (SF2/ASF) and SRSF2 (SC35) using splicing-sensitive arrays and CLIP-seq on mouse embryo fibroblasts (MEFs). Unexpectedly, we find that these SR proteins promote both inclusion and skipping of exons in vivo, but their binding patterns do not explain such opposite responses. Further analyses reveal that loss of one SR protein is accompanied by coordinated loss or compensatory gain in the interaction of other SR proteins at the affected exons. Therefore, specific effects on regulated splicing by one SR protein actually depend on a complex set of relationships with multiple other SR proteins in mammalian genomes. SRSF1 and SRSF2 CLIP-seq
2013-04-05 | E-GEOD-44591 | biostudies-arrayexpress