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Published on: October 11, 2022
Translational unmasking of Emi2 directs cytostatic factor arrest in meiosis II
Jeffrey J Tung1, Kiran Padmanabhan, David V Hansen
1Genentech, Inc., South San Francisco, California, USA.
Abstract:
Cytostatic factor (CSF) arrests unfertilized vertebrate eggs in metaphase of meiosis II by inhibiting the anaphase-promoting complex/cyclosome (APC/C) from mediating cyclin destruction. The APC/C inhibitor Emi2/XErp1 satisfies a number of historical criteria for the molecular identification of CSF, but the mechanism by which CSF is activated selectively in meiosis II is the remaining unexplained criterion. Here we provide an explanation by showing that Emi2 is expressed specifically in meiosis II through translational de-repression or "unmasking" of its mRNA. We find that Emi2 protein is undetectable in immature, G2/prophase-arrested Xenopus oocytes and accumulates approximately 90 minutes after germinal vesicle breakdown. The 3' untranslated region of Emi2 mRNA contains cytoplasmic polyadenylation elements that directly bind the CPEB protein and confer temporal regulation of Emi2 polyadenylation and translation. Our results demonstrate that cytoplasmic polyadenylation and translational unmasking of Emi2 directs meiosis II-specific CSF arrest.
Insights
Cytostatic factor (CSF) arrests eggs in meiosis II by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Emi2 protein unmasking via translational de-repression drives this specific cell cycle arrest.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Cytostatic factor (CSF) is crucial for arresting vertebrate eggs in meiosis II.
- The anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi2/XErp1 is a candidate for CSF.
- The precise mechanism of CSF activation during meiosis II remained unclear.
Purpose of the Study:
- To elucidate the mechanism of selective CSF activation during meiosis II.
- To identify how Emi2/XErp1 mediates the meiosis II arrest.
Main Methods:
- Analysis of Emi2 protein expression timing in Xenopus oocytes.
- Investigating the role of the 3' untranslated region of Emi2 mRNA.
- Studying the interaction between Emi2 mRNA and cytoplasmic polyadenylation element-binding protein (CPEB).
Main Results:
- Emi2 protein is undetectable in immature oocytes and accumulates post-germinal vesicle breakdown.
- The 3' untranslated region of Emi2 mRNA contains regulatory elements.
- CPEB binding to Emi2 mRNA regulates its polyadenylation and translation.
Conclusions:
- CSF arrest in meiosis II is directed by the translational de-repression of Emi2.
- Cytoplasmic polyadenylation and translational unmasking of Emi2 mRNA control CSF activity.
- This mechanism ensures accurate progression through meiosis.
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