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

Author:

Shimada RyukiORCID,Kato Yuzuru,Takeda Naoki,Fujimura Sayoko,Yasunaga Kei-ichiro,Usuki Shingo,Niwa Hitoshi,Araki KimiORCID,Ishiguro Kei-ichiroORCID

Abstract

AbstractMeiosis 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.

Funder

MEXT | Japan Society for the Promotion of Science

Takeda Science Foundation

Japan Agency for Medical Research and Development

Mitsubishi Foundation

Sumitomo Foundation

Naito Foundation

Astellas Foundation for Research on Metabolic Disorders

Uehara Memorial Foundation

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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