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

eLife | 2017

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.

Pubmed ID: 29087293 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM122951
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG004361
  • Agency: NICHD NIH HHS, United States
    Id: P50 HD068158
  • Agency: NICHD NIH HHS, United States
    Id: T32 HD007249

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HTSeq (software resource)

RRID:SCR_005514

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View all literature mentions

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RRID:AB_145841

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RRID:AB_10754785

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