Drosha regulates neurogenesis by controlling neurogenin 2 expression independent of microRNAs.

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 Neurosci

journal_title

Nature neuroscience

authors

Knuckles P,Vogt MA,Lugert S,Milo M,Chong MM,Hautbergue GM,Wilson SA,Littman DR,Taylor V

doi

10.1038/nn.3139

subject

Has Abstract

pub_date

2012-06-17 00:00:00

pages

962-9

issue

7

eissn

1097-6256

issn

1546-1726

pii

nn.3139

journal_volume

15

pub_type

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