Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing
Harvard University · Research Institute of Molecular Pathology · +2 more institutions
Abstract
Dicer is the enzyme that cleaves double-stranded RNA (dsRNA) into 21-25-nt-long species responsible for sequence-specific RNA-induced gene silencing at the transcriptional, post-transcriptional, or translational level. We disrupted the dicer-1 (dcr-1) gene in mouse embryonic stem (ES) cells by conditional gene targeting and generated Dicer-null ES cells. These cells were viable, despite being completely defective in RNA interference (RNAi) and the generation of microRNAs (miRNAs). However, the mutant ES cells displayed severe defects in differentiation both in vitro and in vivo. Epigenetic silencing of centromeric repeat sequences and the expression of homologous small dsRNAs were markedly reduced.…
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- References
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Authors
8- CKChryssa KanellopoulouCorresponding
Harvard University, Research Institute of Molecular Pathology, Dana-Farber Cancer Institute, Vienna Biocenter
- SAStefan A. Muljo
Harvard University, Research Institute of Molecular Pathology, Dana-Farber Cancer Institute, Vienna Biocenter
- ALAndrew L. Kung
Harvard University, Research Institute of Molecular Pathology, Dana-Farber Cancer Institute, Vienna Biocenter
- SGShridar Ganesan
Harvard University, Research Institute of Molecular Pathology, Dana-Farber Cancer Institute, Vienna Biocenter
- RDRonny Drapkin
Harvard University, Research Institute of Molecular Pathology, Dana-Farber Cancer Institute, Vienna Biocenter
Topics & keywords
- Dicer
- Biology
- Gene silencing
- RNA interference
- RNA silencing
- Cell biology
- RNA-induced silencing complex
- Embryonic stem cell
- Life in Land