Abstract:
: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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Knuckles P,Vogt MA,Lugert S,Milo M,Chong MM,Hautbergue GM,Wilson SA,Littman DR,Taylor Vdoi
10.1038/nn.3139subject
Has Abstractpub_date
2012-06-17 00:00:00pages
962-9issue
7eissn
1097-6256issn
1546-1726pii
nn.3139journal_volume
15pub_type
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