STRA8–RB interaction is required for timely entry of meiosis in mouse female germ cells

Ryuki Shimada, Yuzuru Kato, Naoki Takeda, Sayoko Fujimura, Kei-ichiro Yasunaga, Shingo Usuki, Hitoshi Niwa, Kimi Araki and Kei-ichiro Ishiguro ()
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Ryuki Shimada: Kumamoto university
Yuzuru Kato: National Institute of Genetics, Mishima
Naoki Takeda: Kumamoto University
Sayoko Fujimura: Kumamoto University
Kei-ichiro Yasunaga: Kumamoto University
Shingo Usuki: Kumamoto University
Hitoshi Niwa: Kumamoto university
Kimi Araki: Kumamoto University
Kei-ichiro Ishiguro: Kumamoto university

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Meiosis is differently regulated in males and females. In females, germ cells initiate meiosis within a limited time period in the fetal ovary and undergo a prolonged meiotic arrest until puberty. However, how meiosis initiation is coordinated with the cell cycle to coincide with S phase remains elusive. Here, we demonstrate that STRA8 binds to RB via the LXCXE motif. Mutation of the RB-binding site of STRA8 in female mice delays meiotic entry, which consequently delays progression of meiotic prophase and leads to precocious depletion of the oocyte pool. Single-cell RNA-sequencing analysis reveals that the STRA8–RB interaction is required for S phase entry and meiotic gene activation, ensuring precise timing of meiosis initiation in oocytes. Strikingly, the results suggest STRA8 could sequester RB from E2F during pre-meiotic G1/S transition. This study highlights the gene regulatory mechanisms underlying the female-specific mode of meiotic initiation in mice.

Date: 2023
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DOI: 10.1038/s41467-023-42259-6

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