Letter abstract
Nature Genetics 39, 380 - 385 (2007)
Published online: 28 January 2007 | doi:10.1038/ng1969
DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal
Yangming Wang1, Rostislav Medvid1, Collin Melton1, Rudolf Jaenisch2 & Robert Blelloch1
The molecular controls that govern the differentiation of embryonic stem (ES) cells remain poorly understood. DGCR8 is an RNA-binding protein that assists the RNase III enzyme Drosha in the processing of microRNAs (miRNAs), a subclass of small RNAs. Here we study the role of miRNAs in ES cell differentiation by generating a Dgcr8 knockout model. Analysis of mouse knockout ES cells shows that DGCR8 is essential for biogenesis of miRNAs. On the induction of differentiation, DGCR8-deficient ES cells do not fully downregulate pluripotency markers and retain the ability to produce ES cell colonies; however, they do express some markers of differentiation. This phenotype differs from that reported for Dicer1 knockout cells, suggesting that Dicer has miRNA-independent roles in ES cell function. Our findings indicate that miRNAs function in the silencing of ES cell self-renewal that normally occurs with the induction of differentiation.
- Developmental and Stem Cell Biology Program, Department of Urology, University of California, San Francisco, California 94143, USA.
- Whitehead Institute of Biomedical Research, Cambridge, Massachusetts 02142, USA.
Correspondence to: Robert Blelloch1 e-mail: blellochr@stemcell.ucsf.edu
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