Requirement of Drosha in developmental hematopoiesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA674609 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12979467.fastq.gz | Fastqsanger.gz | |||
| SRR12979468.fastq.gz | Fastqsanger.gz | |||
| SRR12979469.fastq.gz | Fastqsanger.gz | |||
| SRR12979470.fastq.gz | Fastqsanger.gz | |||
| SRR12979471_1.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-05 | GSE160832 | GEO
Project description:Using a protein interaction screen, we identify the Microprocessor component Drosha as a novel Dnmt1-interactor. Drosha-deficient ES cells display genomic hypomethylation which is not accounted for by changes in the levels of Dnmt proteins. Both genetic and transfection studies show that Drosha stimulates Dnmt1 methyltransferase activity. We identify two transcripts that are specifically upregulated in Drosha but not Dicer-deficient ES cells. Regions within these transcripts predicted to form stem-loop structures are processed by Microprocessor and can inhibit DNMT1-mediated methylation in vitro. Our results highlight Drosha as a novel regulator of mammalian DNA methylation and we propose that Drosha-mediated processing of RNA is necessary to ensure full Dnmt1 activity. This adds to the Drosha repertoire of non-miRNA dependent functions as well as implicating RNA in regulating Dnmt1 activity and correct levels of genomic methylation.
2017-07-27 | GSE86907 | GEO
Project description:DROSHA complementation experiments were performed to check whether dsRBD of DROSHA recognizes the lower stem of pri-miRNAs and affects miRNA biogenesis.
2018-12-13 | GSE117603 | GEO
Project description:Fetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behaviour in normal and malignant haematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse fetal and adult HSPCs. We defined the redox state of 4455 cysteines in fetal and adult HSPCs and demonstrated a higher susceptibility to oxidation of protein thiols in fetal HSPCs. Our data identified ontogenically active redox switches in proteins with a pronounced role in metabolism and protein homeostasis. Additional redox proteomic analysis identified redox switches acting in mitochondrial respiration as well as protein homeostasis to be triggered during onset of MLL-ENL leukemogenesis in fetal HSPCs. Our data has demonstrated that redox signalling contributes to the regulation of fundamental processes of developmental hematopoiesis and has pinpointed potential targetable redox-sensitive proteins in in utero-initiated MLL-rearranged leukaemia. An H9 human embryonic stem cells cell line was applied to validate data from the primary cells.
2022-06-09 | PXD033115 | Pride
Project description:Neural stem cell regulation is essential for the formation of the central nervous system and homeostatic neurogenesis in the adult mammalian brain. The RNAseIII Drosha, a key component of the miRNA microprocessor, plays a central role in regulating NSC maintenance partially through a miRNA-independent mechanism. Drosha controls mRNA expression levels by targeting and cleaving evolutionary conserved stem-loop hairpins located in the mRNAs of stem cell-related transcription factors. However, it is unknown how the Drosha-mediated endonucleolytic cleavage of mRNA is regulated. Here, we identify novel Drosha and NFIB interactors in hippocampal NSCs by in vitro pull-down assays followed by Mass Spectrometry. We unravel the RNA binding proteins implicated in Drosha-mediated regulation of neurogenesis and we find Scaffold Attachment Factor B1 to play a novel and essential role in NFIB mRNA regulation during neural stem cell differentiation.
2024-06-03 | PXD017677 | Pride
Project description:To investigate the role of amino terminal region (NTR) of Drosha in microprocessor function, we generated amino terminus lacking Drosha (∆N-Drosha) HEK293T cell line by CRISPR-Cas9 genome editing. We then performed miRNA expression profile analysis using data obtained from miRNA-seq of WT-Drosha and ∆N-Drosha containing HEK293T cells.
2023-09-30 | GSE229069 | GEO
Project description:The experiments were conducted to examine the effects of DROSHA mutations on miRNA biogenesis
2023-08-01 | GSE215796 | GEO
Project description:Mutations in Fused in Sarcoma (FUS) gene cause the familial and progressive form of amyotrophic lateral sclerosis (ALS). FUS is a nuclear RNA-binding protein involved in RNA processing and the biogenesis of a specific set of microRNAs. Here we report that Drosha and two previously uncharacterized Drosha-dependent miRNAs are strong modulators of FUS expression and prevent the cytoplasmic segregation of insoluble mutant FUS in vivo. We demonstrate that depletion of Drosha mitigates FUS-mediated degeneration, survival, and motor defects in Drosophila. Mutant FUS strongly interacts with Drosha and causes its cytoplasmic mis-localization into the insoluble FUS inclusions. Reduction in Drosha levels increases the solubility of mutant FUS. Interestingly, we found two Drosha dependent microRNAs, miR-378i and miR-6832-5p, which differentially regulate the expression, solubility, and cytoplasmic aggregation of mutant FUS in iPSC neurons and mammalian cells. More importantly, we report different modes of action of these miRNAs against mutant FUS. Whereas miR-378i may regulate mutant FUS inclusions by preventing G3BP-mediated stress granule formation, miR-6832-5p may affect FUS expression via other proteins or pathways. Overall, our research reveals a possible association between ALS-linked FUS mutations and the Drosha-dependent miRNA regulatory circuit, as well as a useful perspective on potential ALS treatment via microRNAs.
2023-09-09 | GSE242360 | GEO
Project description:MicroRNAs (miRNAs) are a class of small noncoding RNAs about 22-nucleotide (nt) in length that collectively regulate more than 60% of coding genes. Aberrant miRNA expression is associated with numerous diseases, including cancer. miRNA biogenesis is licensed by the ribonuclease (RNase) III enzyme Drosha, the regulation of which is critical in determining miRNA levels. We and others have previously revealed that alternative splicing regulates the subcellular localization of Drosha. To further investigate the alternative splicing landscape of Drosha transcripts, we performed PacBio sequencing in different human cell lines. We identified two novel isoforms resulting from partial intron-retention in the region encoding the Drosha catalytic domain. One isoform (AS27a) generates a truncated protein that is unstable in cells. The other (AS32a) produces a full-length Drosha with a 14 amino acid insertion in the RIIID domain. By taking advantage of Drosha knockout cells in combination with a previously established reporter assay, we demonstrated that Drosha-AS32a lacks cleavage activity. Furthermore, neither Drosha-27a nor Drosha-32a were able to rescue miRNA expression in the Drosha knockout cells. Interestingly, both isoforms were abundantly detected in a wide range of cancer cell lines (up to 15% of all Drosha isoforms). Analysis of the RNA-seq data from over 1000 breast cancer patient samples revealed that the AS32a is relatively more abundant in tumors than in normal tissue, suggesting that AS32a may play a role in cancer development.
2022-01-01 | GSE143169 | GEO
Project description:To determine genes regulated independently of microRNAs in early haematopoietic progenitors (LSKs) we compared the expression profiles of Drosha or Dicer deficient LSKs and control. Those genes differentially expressed between Drosha or Dicer deficient LSKs are likely regulated indepedently of microRNAs as either Drosha or Dicer deletion will lead to a complete and equivalent loss of microRNAs. LSKs were sorted from control, Drosha fl/fl of Dicer fl/fl mice.These cells were activated in vitro for 72 hours to induce total and equivalent deletion of Drosha or Dicer. RNA was extracted after 72 hours.3 repeats of the three groups were analyzed.
2015-09-10 | E-GEOD-61305 | biostudies-arrayexpress