SRSF2 is required for mRNA splicing and spermatogenesis.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA851280 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19761436_1.fastq.gz | Fastqsanger.gz | |||
| SRR19761436_2.fastq.gz | Fastqsanger.gz | |||
| SRR19761437_1.fastq.gz | Fastqsanger.gz | |||
| SRR19761437_2.fastq.gz | Fastqsanger.gz | |||
| SRR19761438_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, is a member of a SRs protein family, which plays significant roles in numerous fundamental biological activities. However, the roles and underlying mechanisms of SRSF2 remain largely unclear during spermatogenesis. Here, we report that SRSF2 is involved in alternative splicing and that male germ cell-specific deletion of Srsf2 by Stra8-GFPCre causes absolute infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 in the male germ cells had harmful influences on the differentiation of spermatogonia and meiosis initiation. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that spermatogenesis, meiotic cell cycle, male gamete generation, reproductive development, and male sex differentiation were involved in the SRSF2 regulatory networks. Furthermore, SRSF2 affects expression and AS of Stra8, Stag3 and Atr in a direct manner, which were critical factors during spermatogenesis. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.
2023-08-18 | GSE206535 | GEO
Project description:Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, is a member of a SRs protein family, which plays significant roles in numerous fundamental biological activities. However, the roles and underlying mechanisms of SRSF2 remain largely unclear during spermatogenesis. Here, we report that SRSF2 is involved in alternative splicing and that male germ cell-specific deletion of Srsf2 by Stra8-GFPCre causes absolute infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 in the male germ cells had harmful influences on the differentiation of spermatogonia and meiosis initiation. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that spermatogenesis, meiotic cell cycle, male gamete generation, reproductive development, and male sex differentiation were involved in the SRSF2 regulatory networks. Furthermore, SRSF2 affects expression and AS of Stra8, Stag3 and Atr in a direct manner, which were critical factors during spermatogenesis. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.
2023-08-18 | GSE206536 | GEO
Project description:SRSF2 is required for mRNA splicing and spermatogenesis [LACE-seq]
| PRJNA851348 | ENA
Project description:SRSF2 is required for mRNA splicing and spermatogenesis [RNA-seq]
| PRJNA851349 | ENA
Project description:BackgroundRNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited.ResultsHere, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner.ConclusionsTaken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.
| S-EPMC10591377 | biostudies-literature
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:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that impacts neurons in the brain and spinal cord. Although a substantial number of studies have been conducted, much remains to be learned about the cellular mechanisms underlying ALS. In this study, we employed an engineered ascorbate peroxidase (APEX)-based proximity biotinylation, together with affinity pull-down of the ensuing biotinylated peptides, to investigate the proximity proteomes of human SOD1 and its two ALS-linked mutants, G85R and G93A. We were able to identify 25 common proteins with preferential enrichment in the proximity proteomes of SOD1G85R and SOD1G93A over wild-type SOD1. Our co-immunoprecipitation and Western blot analyses showed stronger binding of the two SOD1 mutants toward one of these proteins, SRSF2, than the wild-type counterpart. We also observed aberrant RNA splicing of three neurodegeneration-associated and SRSF2-regulated genes, including EIF4A2, SETX, and MELK, in cells with ectopic expression of the two SOD1 mutants relative to cells expressing the wild-type protein. The differences in splicing elicited by the SOD1 variants were markedly attenuated upon knockdown of SRSF2. Collectively, we uncovered that ALS-liked SOD1G85R and SOD1G93A mutants interact more strongly with SRSF2, and the aberrant interactions perturbed mRNA splicing. Thus, our work offered novel mechanistic insights into the contribution of the ALS-linked SOD1 mutants to disease etiology.
2025-06-16 | PXD050785 | Pride
Project description:We report the biological function of Srsf2 in hematopoiesis in conditional knockout mouse models. Ablation of Srsf2 in the hematopoietic lineage caused embryonic lethality, and Srsf2-deficient fetal liver cells showed significantly enhanced apoptosis and decreased hematopoietic stem/progenitor cells. Induced ablation of Srsf2 in adult Mx1Cre/ Srsf2flox/flox mice upon polyinosinic:polycytidylic acid injection demonstrated a significant decrease in lineage-/Sca+/cKit+ cells in bone marrow. To reveal the functional impact of MDS-associated mutations in SRSF2, we profiled global splicing responses on an MDS-L cell line using RASL-seq, and found that the P95H missense mutation and P95 to R102 in-frame 8 amino-acid deletion caused significant changes in alternative splicing. The affected genes were enriched in cancer development and apoptosis. These findings suggest that intact Srsf2 is essential for the functional integrity of the hematopoietic system, and its mutations are likely key driver events to MDS. MDS-L cells (in triplicate) were transfected by srsf2 shRNA only, or pTRIPZ vectors containing both srsf2 shRNA and srsf2 mutants cDNA including P95H and P95 8 amino acid deletion as well as wild-type construct, followed by Dox induction. Total RNAs were extracted and been analyzed by RASL-seq.
2015-03-01 | E-GEOD-61052 | biostudies-arrayexpress
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.
2015-08-10 | GSE71299 | GEO
Project description:We report the biological function of Srsf2 in hematopoiesis in conditional knockout mouse models. Ablation of Srsf2 in the hematopoietic lineage caused embryonic lethality, and Srsf2-deficient fetal liver cells showed significantly enhanced apoptosis and decreased hematopoietic stem/progenitor cells. Induced ablation of Srsf2 in adult Mx1Cre/ Srsf2flox/flox mice upon polyinosinic:polycytidylic acid injection demonstrated a significant decrease in lineage-/Sca+/cKit+ cells in bone marrow. To reveal the functional impact of MDS-associated mutations in SRSF2, we profiled global splicing responses on an MDS-L cell line using RASL-seq, and found that the P95H missense mutation and P95 to R102 in-frame 8 amino-acid deletion caused significant changes in alternative splicing. The affected genes were enriched in cancer development and apoptosis. These findings suggest that intact Srsf2 is essential for the functional integrity of the hematopoietic system, and its mutations are likely key driver events to MDS.
2015-03-01 | GSE61052 | GEO