SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA796353 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17562846_1.fastq.gz | Fastqsanger.gz | |||
| SRR17562846_2.fastq.gz | Fastqsanger.gz | |||
| SRR17562847_1.fastq.gz | Fastqsanger.gz | |||
| SRR17562847_2.fastq.gz | Fastqsanger.gz | |||
| SRR17562848_1.fastq.gz | Fastqsanger.gz |
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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
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.
| S-EPMC8974236 | biostudies-literature
Project description:Elucidating the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can interact with the replication licensing factor MCM2 and inhibit the p53 pathway to maintain the self-renewal and pluripotency of hPSCs. In addition to MCM2, RNA pull-down mass spectrometry showed that ESRG could also bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we show that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG binds to and stabilizes HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encodes E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.
2024-03-05 | GSE236745 | GEO
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
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
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
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 9 samples from three independent experiments using A549 cells transfected with lipofectamine alone, scramble siRNA or SRSF1 siRNA
2013-12-18 | E-GEOD-53410 | biostudies-arrayexpress
Project description:ESRG regulates alternative splicing of TCF3 to maintain hESCs self-renewal and pluripotency
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Project description:Spermatogonial stem cells (SSCs) provide a continuous spermatogenesis and male fertility. However, the underlying mechanisms of alternative splicing (AS) in mouse SSCs are still largely unclear. We demonstrated that SRSF1 is essential for gene expression and splicing in mouse SSCs. Specific deletion of Srsf1 in mouse germ cells impairs self-renewal and homing of SSCs leading to male infertility. Whole-mount staining data showed the absence of germ cells in the testes of adult cKO mice, which indicates severe non-obstructive azoospermia (NOA) in cKO mice. Expression of SSC-related genes (Gfra1, Pou5f1, Plzf, Dnd1, Stra8, and Taf4b) was significantly reduced in the testes of conditional knockout (cKO) mice. CLIP-seq data found that SSC-related genes (Plzf, Id4, Setdb1, Stra8, Tial1, Bcas2, Ddx5, Srsf10, Uhrf1, and Bud31) were bound by SRSF1 in the mouse testes. Moreover, multi-omics analysis suggests that SRSF1 directly binds and regulates the expression of Tial1 via AS to implement SSCs self-renewal and differentiation. Collectively, our data reveal the critical role of an SRSF1-mediated AS in SSCs self-renewal and differentiation, which may provide a framework to elucidate the molecular mechanisms of the post-transcriptional network underlying SSCs.
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Project description:Mllt3 Governs Self-Renewal And Engraftment Of Human Hematopoietic Stem Cells
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