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Double Stranded RNA Binding Protein, Dgcr8, is Essential for microRNA
(miRNA) Processing and Differentiation in Mouse Embryonic Stem Cells
(ESC)
A recent
letter in the March issue of Nature Genetics by researchers at UCSF and
The Whitehead Institute highlights the role for DGCR8, a small RNA
binding protein, in "silencing of embryonic stem cell self renewal."
Along with its microprocessor counterpart, Drosha, Dgcr8 is responsible
for processing long primary miRNAs into short hairpins known as
precursor miRNA, which are eventually exported from the nucleus to the
cytoplasm where they are further processed by Dicer into their final
mature microRNA products. Utilizing floxed Dgcr8 mouse ES cells,
Yangming Wang et al. demonstrated a severe deficiency in biogenesis of
known pre-miRNAs in Dgcr8 knockout ESCs. In addition, Dgcr8 KO ESCs
expressed ESC specific antigens, displayed slower cell population
doubling times, and accumulated in the G1 stage of the cell cycle.
Furthermore, knockout embryos arrested early in development, and
cultured embryoid bodies (EB) displayed marked abnormalities and
reduced differentiation potential when cultured in vitro or injected
into immunodeficient mice. Remarkably, all of these aberrant phenotypes
were rescued by homologous recombination, suggesting that "DGCR8 is
required for the biogenesis of miRNA and that miRNAs are essential for
silencing ES cell self-renewal." These results further suggest that
DICER, previously thought to be miRNA specific, may have additional
unknown roles in the primary differentiation events that occur during
early development. Delineating the specific signaling cascades and
individual players involved in miRNA regulation of ESC self-renewal
could help unravel the intricate nature of how these small RNA products
interact with DNA and proteins to regulate the genome. -Dustin R. Wakeman March 1, 2007ARTICLE: Wang
Y, Medvid R, Melton C, Jaenisch R, Blelloch R. DGCR8 is essential for
microRNA biogenesis and silencing of embryonic stem cell self-renewal.
Nat Genet. 2007 Mar;39(3):380-5.
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