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


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.

SUBMITTER: Shimada R 

PROVIDER: S-EPMC10600341 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Shimada Ryuki R   Kato Yuzuru Y   Takeda Naoki N   Fujimura Sayoko S   Yasunaga Kei-Ichiro KI   Usuki Shingo S   Niwa Hitoshi H   Araki Kimi K   Ishiguro Kei-Ichiro KI  

Nature communications 20231025 1


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 pr  ...[more]

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