DIS3 mediated RNA decay is required for maintenance of spermatogenic lineage in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA664457 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12668157.fastq.gz | Fastqsanger.gz | |||
| SRR12668158.fastq.gz | Fastqsanger.gz | |||
| SRR12668159.fastq.gz | Fastqsanger.gz | |||
| SRR12668160.fastq.gz | Fastqsanger.gz | |||
| SRR12668161.fastq.gz | Fastqsanger.gz |
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Project description:Spermatogonial stem cells (SSCs) self-renewal and differentiation are the foundation for continious spermatognenesis in mice. Here, we investigate the essential role of DIS3 in maintaining SSC homeostasis and facilitating germ cell differentiation to ensure male fertility. Conditional inactivation of DIS3 in male germ cells have severely impaired SSC self-renewal and differentiation, which results in the failure of spermatogenesis associated with a Sertoli cell-only syndrome and adult sterility. RNA-seq analysis reveals that Dis3 deficiency abolishes its nucleolytic activity and causes significant dysregulation of the expression of transcripts in Dis3 mutant testes. We have also found that the pervasive transcription products described previously, such as Promoter Upstream Transcripts (PROMPTs), accumulate robustly upon DIS3 dysfunction in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that DIS3 mutation significantly impairs germline stem cell development that blocks stem cell proliferation and differentiation. Overall, we show that DIS3 ribonuclease plays a critical role in the maintenance of spermatogenic lineage during spermatogenesis in mice.
2021-07-15 | GSE158190 | GEO
Project description:Spermatogonial stem cells (SSCs) self-renewal and differentiation are the foundation for continious spermatognenesis in mice. Here, we investigate the essential role of DIS3 in maintaining SSC homeostasis and facilitating germ cell differentiation to ensure male fertility. Conditional inactivation of DIS3 in male germ cells have severely impaired SSC self-renewal and differentiation, which results in the failure of spermatogenesis associated with a Sertoli cell-only syndrome and adult sterility. RNA-seq analysis reveales that Dis3 deficiency abolishes its nucleolytic activity and causes significant dysregulation of the expression of transcripts in Dis3 mutant testes. We have also found that the pervasive transcription products described previously, such as Promoter Upstream Transcripts (PROMPTs), accumulate robustly upon DIS3 dysfunction in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that DIS3 mutation significantly impairs germline stem cell development that blocks stem cell proliferation and differentiation. Overall, we show that DIS3 ribonuclease plays a critical role in the maintenance of spermatogenic lineage during spermatogenesis in mice.
2020-08-20 | GSE156505 | GEO
Project description:DIS3 ribonuclease is required for the maintenance of spermatogenic lineage in mice
| PRJNA658132 | ENA
Project description:Somatic mutations affecting DIS3, the catalytic component of the RNA exosome, have been found in up to 18% of patients affected by the hematological cancer multiple myeloma. Here we show that DIS3 targets and degrades the pluripotency factor LIN28B. In cancer cells, DIS3 inactivation leads to enhanced LIN28B expression, thus disrupting the let-7 miRNAs tumor suppressor network and ultimately increasing protein levels of crucial oncogenes such as MYC and RAS. DIS3 represents the catalytic component of the exosome. The exosome is required for cell viability and targets several RNA species, including pre-mRNAs, pre-tRNAs, pre-rRNAs, snRNAs and snoRNAs. To gain insight on the macular wiring underlying DIS3 activity in mammalian cells, we comprehensively evaluated expression profiles, including miRNAs, in various cell lines, upon DIS3 knockdown.
2015-06-12 | GSE55246 | GEO
Project description:Somatic mutations affecting DIS3, the catalytic component of the RNA exosome, have been found in up to 18% of patients affected by the hematological cancer multiple myeloma. Here we show that DIS3 targets and degrades the pluripotency factor LIN28B. In cancer cells, DIS3 inactivation leads to enhanced LIN28B expression, thus disrupting the let-7 miRNAs tumor suppressor network and ultimately increasing protein levels of crucial oncogenes such as MYC and RAS. DIS3 represents the catalytic component of the exosome. The exosome is required for cell viability and targets several RNA species, including pre-mRNAs, pre-tRNAs, pre-rRNAs, snRNAs and snoRNAs. To gain insight on the macular wiring underlying DIS3 activity in mammalian cells, we comprehensively evaluated expression profiles, including miRNAs, in various cell lines, upon DIS3 knockdown. This series of microarray experiments contains the miRNA expression profiles of independent replicates of RPMI-8226, KMS12-BM multiple myeloma cell lines and HEK-293T cells, knocked-down with a scrambled or hDIS3 sh4 and collected 72 hours after infection. 500 nanograms of total RNA were processed using the FlashTag labeling kit, which uses a tailing reaction followed by ligation of the biotinylated signal molecule to the target RNA sample. The labelled RNA was then hybridized to Affymetrix GeneChip® microRNA arrays v1.0, following the Affymetrix manufacturer's instructions.
2015-06-12 | E-GEOD-55246 | biostudies-arrayexpress
Project description:Conditional inactivation of DIS3 in spermatocytes impairs meiotic progression and causes defective spermatogenesis in mice. scRNA-seq analysis indicates that DIS3 mutation significantly impairs spermatocytes meiotic progression and dysregulates transcriptome in spermatocytes. We show that DIS3 ribonuclease plays critical roles in male meiotic progression and spermatogenesis in mice.
2024-12-13 | GSE274927 | GEO
Project description:Human DIS3 is a nuclear, catalytic subunit of the exosome complex containing exonucleolytic and endonucleolytic active domains. To identify DIS3 targets genome-wide we conducted comprehensive transcriptomic analysis of HEK293 cells producing mutated DIS3 versions and Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) experiments. Pervasive transcription products like Promoter Upstream Transcripts (PROMPTs) accumulated robustly in catalytic DIS3 mutants, representing ~8% of PAR-CLIP reads. Importantly, RNAs originating from unannotated genomic regions increased ~2.5 times in double DIS3 mutants, covering ~70% of genome and allowing for discovery of thousands of novel transcripts. The first intron of many pre-mRNAs accumulated in DIS3 mutants indicating a widespread premature RNA polymerase II termination. The short form of NEAT1 lincRNA was overexpressed in DIS3 mutants, leading to increased number of paraspeckles. Moreover, there was a global deregulation of mRNAs in DIS3 double mutant. Finally, snoRNA precursors accumulated, which correlated with a strong PAR-CLIP signal indicating that DIS3 but not RRP6 is a main snoRNA processing enzyme. In aggregate, we demonstrate that DIS3 is a major nucleoplasmic activity responsible for shaping the human transcriptome.
2015-08-20 | GSE64332 | GEO
Project description:Male germ cell meiosis is essential for generating haploid spermatozoa in mice. Here, we investigate the essential role of DIS3 in male germ cell meiosis in mice. Conditional inactivation of DIS3 in spermatocytes with Stra8-cre transgenic mice have severely impaired meiotic progression, which results in defective meiosis and spermatogenesis. RNA-seq analysis reveals that Dis3 deficiency causes significant dysregulation of the expression of transcripts in mutant testes. Meiosis-associated genes are significantly decreased in the absence of DIS3. Therefore, we show that DIS3 ribonuclease plays a critical role in germ cell meiosis during spermatogenesis in mice.
2021-07-16 | GSE180197 | GEO
Project description:The recently proposed exozyme hypothesis posits that subunits of the RNA processing exosome assemble into structurally distinct protein complexes that function in disparate cellular compartments and RNA metabolic pathways. Here, in a genetic test of this hypothesis, we examine the role of Dis3 -- an essential polypeptide with endo- and 3' to 5' exo-ribonuclease activity -- in cell cycle progression. We present several lines of evidence that perturbation of DIS3 affects microtubule (MT) localization and structure in Saccharomyces cerevisiae. Cells with a DIS3 mutation: (i) accumulate anaphase and pre-anaphase mitotic spindles; (ii) exhibit spindles that are mis-oriented and displaced from the bud neck; (iii) harbor elongated spindle-associated astral MTs; (iv) have an increased G1 astral MT length and number; and (v) are hypersensitive to MT poisons. Mutations in the core exosome genes RRP4 and MTR3 and the exosome cofactor gene MTR4 -- but not other exosome subunit gene mutants -- also elicit MT phenotypes. RNA deep sequencing analysis (RNA-seq) shows broad changes in the levels of cell cycle- and microtubule-related transcripts in mutant strains. Collectively, the different mitotic phenotypes and distinct sets of mRNAs affected by the exosome subunit and cofactor mutants studied here suggest that Dis3 has a core exosome-independent role(s) in cell cycle progression. These observations are consistent with the predictions of the exozyme hypothesis and also suggest an evolutionarily conserved role for Dis3 in linking RNA metabolism, MTs, and mitotic progression. RNA-seq analysis of total RNA harvested from WT, mtr3-1, mtr4-1, and Dis3^mtr (rrp44-1/mtr17-1) Saccharomyces cerevisiae strains after a temperature shift.
2013-01-01 | E-GEOD-29018 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs) are frequently generated during splicing. Their physiological roles, however, remain largely elusive. Some specific circRNAs function as microRNA (miRNA) or RNA binding protein (RBP) sponges or encode for proteins and are actively translated. Due to the lack of accessible ends, circRNAs are resistant to exonucleolytic cleavage and thus are more stable than linear RNAs. Nevertheless, circRNAs are most likely turned over by cellular degradation pathways. Here, we used a biochemical purification strategy to find nucleases that could degrade circRNAs. We identified the exosome-associated nuclease DIS3, which contains an endonucleolytic PIN domain and an exonuclease domain. We show that DIS3 can degrade circRNAs independently of the exosome in vitro. Although moderately, RNA-seq reveals that selected circRNAs are stabilized when DIS3 is reduced in vivo. Based on our data, we propose a model, in which cytoplasmic DIS3 contributes to the turnover of circRNAs in human cells.
2025-05-05 | PXD050442 | Pride