DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal

Nat Genet. 2007 Mar;39(3):380-5. doi: 10.1038/ng1969. Epub 2007 Jan 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / metabolism*
  • Phenotype
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA-Binding Proteins
  • Ribonuclease III / metabolism


  • Dgcr8 protein, mouse
  • MicroRNAs
  • Proteins
  • RNA-Binding Proteins
  • Endoribonucleases
  • Dicer1 protein, mouse
  • Drosha protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE6586