Mus musculus
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REPOSITORIES: ENA
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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
Project description:The DNA damage response (DDR) is the signaling cascade that recognizes DNA double-strand breaks (DSB) and promotes their resolution via the DNA repair pathways of Non-Homologous End Joining (NHEJ) or Homologous Recombination (HR). We and others have shown that DDR activation requires DROSHA. However, whether DROSHA exerts its functions by associating with damage sites, what controls its recruitment and how DROSHA influences DNA repair, remains poorly understood. Here we show that DROSHA associates to DSBs independently from transcription. Neither H2AX, nor ATM nor DNA-PK kinase activities are required for its recruitment to break site. Rather, DROSHA interacts with RAD50 and inhibition of MRN by Mirin treatment abolishes this interaction. MRN inactivation by RAD50 knockdown or mirin treatment prevents DROSHA recruitment to DSB and, as a consequence, also 53BP1 recruitment. During DNA repair, DROSHA inactivation reduces NHEJ and boosts HR frequency. Indeed, DROSHA knockdown also increase the association of downstream HR factors such as RAD51 to DNA ends. Overall, our results demonstrate that DROSHA is recruited at DSBs by the MRN complex and direct DNA repair toward NHEJ.
2021-03-15 | GSE166631 | GEO
Project description:The endonuclease Dicer is a key component of the human RNA interference (RNAi) pathway and known for its role in cytoplasmic micro RNA (miRNA) production. Recent findings suggest that non-canonical Dicer generates small non-coding RNA (ncRNA) to mediate the DNA damage response (DDR). Here we show that human Dicer is phosphorylated in the platform-PAZ-connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks (DSBs). We further demonstrate that turnover of damage-induced nuclear dsRNA requires additional phosphorylation of carboxy-terminal Dicer residues (S1728 and S1852). DNA damage-induced nuclear Dicer accumulation is conserved in mammals. Dicer depletion causes spontaneous DNA damage and delays DNA repair. Taken together, we place Dicer in context of the DDR by demonstrating DNA damage-inducible phospho-switch that causes localised processing of nuclear dsRNA by p-Dicer to promote DNA repair.
2018-12-08 | GSE75892 | 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.
2015-09-10 | GSE61305 | GEO
Project description:Here we analyze the small RNA species in the following: 1. DN3 thymocytes following inactivation of LoxP flanked Drosha and Dicer alleles with Lck-cre 2. Tregs following inactivation of LoxP flanked Drosha and Dicer alleles with CD4-cre 3. activated CD4+ T cells following inactivation of LoxP flanked Drosha and Dicer alleles with CD4-cre 4. MEFs following inactivation of LoxP flanked Drosha and Dicer alleles with Rosa26-CreER and 4-OH tamoxifen treatment
2010-08-18 | GSE22760 | GEO
Project description:We performed small RNA sequencing in breast cancer cells treated with siRNA for Control, DCGR8, DROSHA, TARBP2, DICER
2018-11-07 | GSE114773 | GEO
Project description:RNA sequencing was performed comparing sciatic nerves of Schwann cell specific DICER mutants with SC-specific DGCR8 and DROSHA mutants.
2018-10-08 | GSE64880 | GEO
Project description:Here we analyze the small RNA species in the following: 1. DN3 thymocytes following inactivation of LoxP flanked Drosha and Dicer alleles with Lck-cre 2. Tregs following inactivation of LoxP flanked Drosha and Dicer alleles with CD4-cre 3. activated CD4+ T cells following inactivation of LoxP flanked Drosha and Dicer alleles with CD4-cre 4. MEFs following inactivation of LoxP flanked Drosha and Dicer alleles with Rosa26-CreER and 4-OH tamoxifen treatment Fractionation of small RNAs (19-30nt) and cloning of only RNA with 5' phosphates and 3' hydroxyls
2010-08-18 | E-GEOD-22760 | biostudies-arrayexpress
Project description:Recent studies suggest that the repair of DNA double-strand breaks (DSBs) is supported by damage-induced small RNAs (diRNAs) that are generated by Drosha and Dicer from transcripts that originate from the regions flanking the break. However, transcription and diRNA production at naturally occurring DSBs in mammalian genomes remain controversial. We have used the homing endonuclease I-PpoI to produce DSBs in human and mouse cells, and we have analyzed the biogenesis of diRNAs at I-PpoI induced breaks in the 28S rDNA and the Ryr2 gene. We provide direct evidence that RNA polymerase II transcribes the sequences that flank the DSBs. Our results also reveal that the resulting transcripts are processed into two types of diRNAs with characteristic length and terminal nucleotide signatures. Furthermore, diRNA production is independent of Drosha and DGCR8, and only a subset of diRNAs depends on Dicer, as shown by small RNA analyses of knock-out cells that lack specific RNA processing enzymes. Our findings are compatible with previous observations of a general transcription inhibition at DSBs and provide novel insights into the mechanisms of RNA synthesis and processing at DSBs.
2018-10-22 | GSE106764 | GEO
Project description:Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage
| PRJNA305622 | ENA