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Updated: Jul 3, 2026

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
CDC2A (CDK1)-mediated phosphorylation of MSY2 triggers maternal mRNA degradation during mouse oocyte maturation
Sergey Medvedev1, Juxiang Yang, Norman B Hecht
1Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract:
Degradation of maternal mRNA is thought to be essential to undergo the maternal-to-embryonic transition. Messenger RNA is extremely stable during oocyte growth in mouse and MSY2, an abundant germ cell-specific RNA-binding protein, likely serves as a mediator of global mRNA stability. Oocyte maturation, however, triggers an abrupt transition in which most mRNAs are significantly degraded. We report that CDC2A (CDK1)-mediated phosphorylation of MSY2 triggers this transition. Injecting Cdc2a mRNA, which activates CDC2A, overcomes milrinone-mediated inhibition of oocyte maturation, induces MSY2 phosphorylation and the maturation-associated degradation of mRNAs. Inhibiting CDC2A following its activation with roscovitine inhibits MSY2 phosphorylation and prevents mRNA degradation. Expressing non-phosphorylatable dominant-negative forms of MSY2 inhibits the maturation-associated decrease in mRNAs, whereas expressing constitutively active forms induces mRNA degradation in the absence of maturation and phosphorylation of endogenous MSY2. A positive-feedback loop of CDK1-mediated phosphorylation of MSY2 that leads to degradation of Msy2 mRNA that in turn leads to a decrease in MSY2 protein may ensure that the transition is irreversible.
Insights
Maternal messenger RNA (mRNA) stability during oocyte maturation is regulated by MSY2 protein phosphorylation. This phosphorylation, triggered by CDC2A (CDK1), initiates the degradation of maternal mRNA, essential for embryonic development.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Developmental Biology
Background:
- Maternal mRNA degradation is crucial for the maternal-to-embryonic transition.
- MSY2, an RNA-binding protein, maintains mRNA stability during oocyte growth.
- Oocyte maturation involves a significant degradation of most maternal mRNAs.
Purpose of the Study:
- To investigate the role of MSY2 phosphorylation in maternal mRNA degradation during oocyte maturation.
- To identify the kinase responsible for MSY2 phosphorylation and its role in the maternal-to-embryonic transition.
Main Methods:
- In vitro oocyte maturation assays.
- Manipulation of CDC2A (CDK1) activity via mRNA injection and roscovitine inhibition.
- Expression of dominant-negative and constitutively active MSY2 variants.
- Analysis of mRNA levels and MSY2 phosphorylation status.
Main Results:
- CDC2A (CDK1)-mediated phosphorylation of MSY2 triggers the degradation of maternal mRNAs during oocyte maturation.
- Inhibition of CDC2A prevents MSY2 phosphorylation and subsequent mRNA degradation.
- Non-phosphorylatable MSY2 inhibits mRNA decrease, while active MSY2 induces degradation independently of maturation.
- A positive-feedback loop involving MSY2 phosphorylation and Msy2 mRNA degradation ensures an irreversible transition.
Conclusions:
- MSY2 phosphorylation by CDC2A (CDK1) is the key event initiating maternal mRNA degradation for the maternal-to-embryonic transition.
- This phosphorylation event is tightly regulated and essential for successful embryonic development.
- A feedback mechanism involving MSY2 and its own mRNA ensures the completion of this critical developmental transition.
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