The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline

Elife. 2017 Oct 31:6:e26116. doi: 10.7554/eLife.26116.


The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn homolog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.

Keywords: Bgcn; YTHDC2; developmental biology; germline stem cell lineage; mitosis to meiosis transition; mouse; post-transcriptional regulation; spermatogenesis; stem cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Proliferation*
  • Gene Expression Regulation
  • Germ Cells / enzymology*
  • Germ Cells / physiology*
  • Meiosis
  • Mice
  • Mitosis
  • Protein Binding
  • RNA Helicases / metabolism*


  • RNA Helicases
  • Ythdc2 protein, mouse