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SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [RNA-Seq]

ABSTRACT: Alternative splicing (AS) plays significant roles in fundamental biological activities. AS also are prevalent in the testis, but the regulations of alternative splicing in spermatogenesis is vague. Here, we report that Serine/arginine-rich splicing factor 1 (SRSF1), plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf1 led to complete infertility and abnormal spermatogenesis. We further demonstrated that Srsf1 is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF1 regulatory networks have functions in spermatogenesis. Particularly, we found that SRSF1 affects the AS of Stra8 in a direct manner and Dazl, Dmc1, Mre11a, Syce2 and Rif1 in an indirect manner. Taken together, our findings demonstrate that SRSF1 has crucial functions in spermatogenesis and male fertility by regulating alternative splicing.

ORGANISM(S): Mus musculus

PROVIDER: GSE226550 | GEO | 2024/03/31

REPOSITORIES: GEO

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SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [LACE-seq]

Project description:Alternative splicing (AS) plays significant roles in fundamental biological activities. AS also are prevalent in the testis, but the regulations of alternative splicing in spermatogenesis is vague. Here, we report that Serine/arginine-rich splicing factor 1 (SRSF1), plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf1 led to complete infertility and abnormal spermatogenesis. We further demonstrated that Srsf1 is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF1 regulatory networks have functions in spermatogenesis. Particularly, we found that SRSF1 affects the AS of Stra8 in a direct manner and Dazl, Dmc1, Mre11a, Syce2 and Rif1 in an indirect manner. Taken together, our findings demonstrate that SRSF1 has crucial functions in spermatogenesis and male fertility by regulating alternative splicing.

2024-03-31 | GSE226551 | GEO

SRSF2 is required for mRNA splicing and spermatogenesis [LACE-seq]

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

SRSF2 is required for mRNA splicing and spermatogenesis [RNA-seq]

2023-08-18 | GSE206535 | GEO

Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice

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.

2024-01-08 | GSE227575 | GEO

SRSF1 is crucial for male meiosis through alternative splicing during homologous pairing and synapsis in mice [RNA-seq]

Project description:Homologous pairing and synapsis are essential in meiotic prophase I during spermatogenesis. However, the underlying mechanisms of how alternative splicing (AS) functions in homologous pairing and synapsis remain largely unclear. We reveal that SRSF1 is essential for gene expression and AS in homologous pairing and synapsis. Conditional knockout (cKO) of Srsf1 in mouse germ cells impaired homologous pairing and synapsis, leading to non-obstructive azoospermia (NOA). SRSF1 was required for initial homology recognition, telomere-led chromosome movement, and synaptonemal complex (SC) assembly. Moreover, SRSF1 interacted with TRA2B and U2AF2, directly binding and regulating the expression of Dmc1, Sycp1, Sun1, and Majin via AS to implement homologous pairing and synapsis during the meiotic prophase I program. Altogether, our data reveal the critical role of an SRSF1-mediated post-transcriptional regulatory mechanism in homologous pairing and synapsis during meiotic prophase I, providing a framework for elucidating the molecular mechanisms underlying the post-transcriptional network of male meiosis.

2024-01-09 | GSE227403 | GEO

SRSF1 is crucial for male meiosis through alternative splicing during homologous pairing and synapsis in mice [CLIP-seq]

2024-01-08 | GSE227303 | 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

SRSF1 regulates primordial follicle formation and number determination during meiotic prophase I

Project description:Serine/arginine-rich splicing factor 1 (SRSF1; previously SF2/ASF) is a pivotal posttranscriptional regulator of gene expression in various biological processes. However, the physiological roles and mechanism of SRSF1 in mouse early-stage oocytes remain elusive. Here we show that SRSF1 is essential for primordial follicle formation and number determination during meiotic prophase I. The conditional knockout of Srsf1 in mouse oocytes impairs primordial follicle formation and leads to primary ovarian insufficiency (POI). Oocyte-specific genes (e.g., LHX8, NOBOX, SOHLH1, SOHLH2, FIGLA, KIT, JAGGED1, and RAC1) that regulate primordial follicle formation are suppressed in newborn Stra8-GFPCre Srsf1Fl/Fl (cKO) mouse ovaries. However, meiotic defects are the leading cause of abnormal primordial follicle formation. In cKO mouse ovaries, immunofluorescence results suggest that the failure of synapsis and the inability to undergo recombination result in fewer homologous DNA crossovers (COs). Moreover, SRSF1 directly binds and regulates the expression of the POI-related genes Six6os1 and Msh5 via alternative splicing to implement the meiotic prophase I program. Altogether, our data reveal a critical role of the SRSF1-mediated posttranscriptional regulatory mechanism in the mouse oocyte meiotic prophase I program, which provides a framework to elucidate molecular mechanisms of the posttranscriptional network underlying primordial follicle formation.

2023-02-06 | GSE198205 | GEO

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 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

Chip-chip from Mouse MEFs cells for H3K36me3, Srsf1, Psip1(A300-847 antibody).

Project description:The p52 isoform of Psip1/Ledgf links histone H3K36 methylation and the regulation of alternative splicing. Chromatin immunoprecipitation (ChIP) of Psip1 together with H3K36me3 and Srsf1 and by ChIP-on-chip analysis demonstrated that H3K36me3, Psip1 and SRSF1 enrichment correlates on the gene bodies Array design includes 2 dye swap replicates for Srsf1 and Psip1-/- samples, and single arrays for PSIP and H3K36me3 samples

2012-01-01 | E-GEOD-31520 | biostudies-arrayexpress

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