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Updated: Feb 24, 2026

Microscopy of Fission Yeast Sexual Lifecycle
Published on: March 9, 2016
Ubiquitination-dependent control of sexual differentiation in fission yeast
Fabrizio Simonetti1,2, Tito Candelli1,2, Sebastien Leon3
1Institut Jacques Monod, Team "Metabolism and Function of RNA in the Nucleus", CNRS, UMR7592, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Abstract:
In fission yeast, meiosis-specific transcripts are selectively eliminated during vegetative growth by the combined action of the YTH-family RNA-binding protein Mmi1 and the nuclear exosome. Upon nutritional starvation, the master regulator of meiosis Mei2 inactivates Mmi1, thereby allowing expression of the meiotic program. Here, we show that the E3 ubiquitin ligase subunit Not4/Mot2 of the evolutionarily conserved Ccr4-Not complex, which associates with Mmi1, promotes suppression of meiotic transcripts expression in mitotic cells. Our analyses suggest that Mot2 directs ubiquitination of Mei2 to preserve the activity of Mmi1 during vegetative growth. Importantly, Mot2 is not involved in the constitutive pathway of Mei2 turnover, but rather plays a regulatory role to limit its accumulation or inhibit its function. We propose that Mmi1 recruits the Ccr4-Not complex to counteract its own inhibitor Mei2, thereby locking the system in a stable state that ensures the repression of the meiotic program by Mmi1.
Insights
The Ccr4-Not complex subunit Mot2 ubiquitinates Mei2, preserving Mmi1 activity and suppressing meiotic gene expression in fission yeast during vegetative growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Meiosis-specific transcripts are degraded in vegetative fission yeast by Mmi1 and the nuclear exosome.
- Mei2 inactivates Mmi1 upon starvation, enabling meiotic gene expression.
Purpose of the Study:
- To investigate the role of the Ccr4-Not complex subunit Mot2 in regulating meiotic gene expression during vegetative growth in fission yeast.
Main Methods:
- Biochemical assays to study protein-protein interactions.
- Ubiquitination assays to assess Mei2 modification.
- Analysis of meiotic transcript levels in wild-type and mutant strains.
Main Results:
- Mot2 associates with Mmi1 and promotes the suppression of meiotic transcripts in mitotic cells.
- Mot2 directs the ubiquitination of Mei2, preserving Mmi1 activity.
- Mot2's role is regulatory, limiting Mei2 accumulation or function, not constitutive turnover.
Conclusions:
- Mmi1 recruits the Ccr4-Not complex (including Mot2) to ubiquitinate and inhibit Mei2.
- This mechanism ensures stable repression of the meiotic program during vegetative growth.
- Mot2 plays a crucial regulatory role in the Mmi1-Mei2 axis.
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