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Identification of alternative splicing events regulated by the splicing factor SRSF1 using data from exon-junction microarray technologies

ABSTRACT: Analysis to identify genome-wide differential alternative splicing events in A549 cells in which the levels of the gene SRSF1 were down-regulated with a specific siRNA 9 samples from three independent experiments using A549 cells transfected with lipofectamine alone, scramble siRNA or SRSF1 siRNA

ORGANISM(S): Homo sapiens

SUBMITTER: Ravi Sharma

PROVIDER: E-GEOD-53410 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Identification of alternative splicing events regulated by the splicing factor SRSF1 using data from exon-junction microarray technologies

Project description:Analysis to identify genome-wide differential alternative splicing events in A549 cells in which the levels of the gene SRSF1 were down-regulated with a specific siRNA

2013-12-18 | GSE53410 | GEO

Splicing factor SRSF1 promotes breast cancer progression via regulating alternative splicing

Project description:Purpose:Intensive evidence have highlighted the effect of aberrant alternative splicing (AS) events triggered by dysregulation of SR protein family on cancer progression. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods:We conducted comprehensive analysis for the expression and the clinical correlation of SRSF1 in BRCA based on TCGA, Metabric database, clinical tissue samples and BRCA cell lines. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and its binding motif were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. Finally, the expression and their clinical significance were validated in clinical samples and TCGA database. Results:SRSF1 was upregulated in BRCA samples, associated positively with tumor grade and Ki-67 index, and correlated with poor prognosis in hormone receptor positive (HR+) cohort, which facilitated tumor progression in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of PTPMT1. Furthermore, PTPMT1 splice switching regulated by SRSF1 partially mediated the oncogenic role of SRSF1 via the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients. Conclusions:Collectively, SRSF1 exerts the oncogenic roles in BRCA partially through regulating AS of PTPMT1, which could be a candidate prognostic factor and therapeutic target in HR+ BRCA cohort.

2021-05-25 | GSE163025 | GEO

SRSF1 role in cellular gene expression and splicing

Project description:SRSF1 is an abundant RNA-binding protein with functions in mRNA splicing, stability, translation and transcription of cellular and viral genes. We analyzed the role that SRSF1 plays in cellular gene transcription and splicing by transfecting HEK293 cells with a SRSF1 expression plasmid and by analyzing the transcriptome of the transiently transfected cells 15 hrs and 48 hrs post transfection. We also explored the role of the SRSF1 domains by transfecting a deletion clone of SRSF1 carrying only the RNA Recognition Motifs 1 and 2 (RRM1,2) but not the Arg-Ser rich (SR) domain.

2019-03-20 | GSE124397 | GEO

Identification of alternative splicing changes upon ablation of cytoplasmic SRSF1.

Project description:SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in Srsf1 to create a mouse model harboring a non-shuttling SRSF1 protein. We then assessed whether alblation of shuttling activities of SRSF1 affects its nuclear functions.

2021-08-05 | GSE157269 | GEO

SRSF1 is involved in alternative mRNA splicing in granulosa cell survival

Project description:Granulosa cells abnormalities are one of the characteristics of premature ovarian insufficiency (POI). Abnormal expression of serine/arginine-rich splicing factor 1 (SRSF1) can causes a variety of diseases, but the role of SRSF1 in mouse granulosa cells has been poorly reported. In this study, we found that SRSF1 was expressed in the nuclei of both mouse oocytes and granulosa cells. Specific knockout of SRSF1 in granulosa cells was performed using Foxl2-creERT2 mice, and morphological staining showed that follicular development was blocked. In addition, granulosa cell proliferation decreased and cell apoptosis increased. The differential gene Gene Ontology (GO) analysis of RNA-Seq results showed abnormal expression of DNA repair, cell killing and other signaling pathways. Alternative splicing (AS) analysis showed that SRSF1 affected DNA damage in granulosa cells by regulating genes related to DNA repair. In conclusion, SRSF1 in granulosa cells affects female reproduction by controlling the development of follicles through regulating granulosa cell DNA repair related genes.

2024-01-01 | GSE228975 | GEO

Effect of SRSF1 depletion on FANCD2 mRNA and isoform expression and effect of FANCD2 depletion or expression of SRSF1 mutants on splicing

Project description:To investigate the cooperative function of FANCD2/SRSF1 complex in the regulation of R-loops, we performed gene expression, isoform and splicing analysis in Hela cells depleted of SRSF1 or expressing SRSF1 mutants and FA-D2 mutant (FA-D2) and wild type (FA-D2+FANCD2) cells.

2024-02-26 | GSE212471 | GEO

Translational activity of the splicing factor SRSF1 is required for development and cilia function

Project description:The SR protein family of splicing factors regulate constitutive and alternative pre-mRNA splicing. A subset of them, including SRSF1, shuttles continuously between the nucleus and cytoplasm affecting post-splicing processes. We have previously identified a role for SRSF1 in promoting the translation of specific mRNA transcripts, particularly those encoding centrosomal proteins. Here, we used CRISPR/Cas9 editing to knock-in a nuclear retention signal (NRS) in Srsf1 resulting in a non-shuttling SRSF1 mouse model (Srsf1NRS). Srsf1NRS/NRS mice displayed small body size, hydrocephaly and male infertility, all associated with ciliary defects. We observed reduced translation of thousands of mRNAs, in particular of ciliary components, in cells derived from this model. Consistently, we found that the lack of cytoplasmic SRSF1 led to decreased abundance of proteins involved in multiciliogenesis and affected ciliary structure and motility in multiciliated cells. Altogether, these results highlight the physiological relevance of the activity of a splicing factor in the cytoplasm.

2021-08-06 | PXD019859 | Pride

The splicing factor SRSF1 regulates the radio-resistance of cancer cells through modulating the alternative splicing of PTPMT1

Project description:RNA-seq was performed on H1299 cells that stably knocking down SRSF1 or control, as well as these cells that were treated with ionizing radiation, in order to profile the alternative splicing events that were regulated by SRSF1 upon ionizing radiation.

2018-11-12 | GSE107224 | GEO

Splicing Factor SRSF1 Promotes Tumorigenesis via Oncogenic Splice-Switching and Predicts Poor Prognosis in Multiple Myeloma

Project description:Alternative splicing (AS) and its regulation play critical roles in cancer, yet the dysregulation of AS and its molecular bases in multiple myeloma (MM) development have not yet been elucidated. We identified SRSF1 as a key splicing factor in tumor progression, SRSF1 expression was frequently upregulated in MM and correlated with poor survival.We conducted transcriptome comparison of SRSF1-knockdown and control cells highlighted the functional importance of SRSF1 in mediating MM progression through regulating AS, and revealed the upstream and downstream molecular regulation mechanism of SRSF1. Further investigation to clarify molecular mechanisms and to replicate our findings is necessary. Thus, our findings are of high translational relevance and are expected to have a substantial impact on the development of a promising epigenetic approach for investigating targeted therapies for MM with high SRSF1 expression.

2022-09-04 | GSE160724 | GEO

SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal

Project description:Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing factor family are major splicing regulators that are broadly required for organ development as well as cell and organism viability. However, how these proteins support adult organ function remains largely unknown. Here, we used the continuously growing mouse incisor as a model to dissect the functions of the prototypical SR-family protein SRSF1 during tissue homeostasis and renewal. We identified an SRSF1-governed alternative splicing network that is specifically required for dental proliferation and survival of progenitors but dispensable for the viability of differentiated cells. We also observed a similar progenitor-specific role of SRSF1 in the small intestinal epithelium, indicating a conserved function of SRSF1 across adult epithelial tissues. Thus, our findings define a regulatory mechanism by which SRSF1 specifically controls progenitor-specific alternative splicing events to support adult tissue homeostasis and renewal.

2022-01-18 | GSE193492 | GEO

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