Drosha regulates neurogenesis by controlling Neurogenin 2 expression independent of microRNAs
doi: 10.1038/nn.3139
pmid: 22706270
Drosha regulates neurogenesis by controlling Neurogenin 2 expression independent of microRNAs
Temporal regulation of embryonic neurogenesis is controlled by hypostable transcription factors. The mechanism of the process is unclear. Here we show that the RNase III Drosha and DGCR8 (also known as Pasha), key components of the microRNA (miRNA) microprocessor, have important functions in mouse neurogenesis. Loss of microprocessor in forebrain neural progenitors resulted in a loss of stem cell character and precocious differentiation whereas Dicer deficiency did not. Drosha negatively regulated expression of the transcription factors Neurogenin 2 (Ngn2) and NeuroD1 whereas forced Ngn2 expression phenocopied the loss of Drosha. Neurog2 mRNA contains evolutionarily conserved hairpins with similarities to pri-miRNAs, and associates with the microprocessor in neural progenitors. We uncovered a Drosha-dependent destabilization of Neurog2 mRNAs consistent with microprocessor cleavage at hairpins. Our findings implicate direct and miRNA-independent destabilization of proneural mRNAs by the microprocessor, which facilitates neural stem cell (NSC) maintenance by blocking accumulation of differentiation and determination factors.
- New York University United States
- Max Planck Society Germany
- University of Sheffield United Kingdom
- National Institute for Health Research United Kingdom
- Walter and Eliza Hall Institute of Medical Research Australia
Mice, Knockout, Ribonuclease III, Neurogenesis, Nerve Tissue Proteins, Mice, Inbred C57BL, Mice, MicroRNAs, Gene Expression Regulation, Neural Stem Cells, Pregnancy, Basic Helix-Loop-Helix Transcription Factors, Animals, Female, Cells, Cultured
Mice, Knockout, Ribonuclease III, Neurogenesis, Nerve Tissue Proteins, Mice, Inbred C57BL, Mice, MicroRNAs, Gene Expression Regulation, Neural Stem Cells, Pregnancy, Basic Helix-Loop-Helix Transcription Factors, Animals, Female, Cells, Cultured
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