Nat Commun 2025 Dec 12;171:720. doi: 10.1038/s41467-025-67476-z.

Natural degradation of RNA polymerase II is essential for oocyte chromatin reorganization and maternal-to-zygotic transition.

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The final step of oocyte growth, which reorganizes chromatin from the non-surrounded nucleolus (NSN) to the surrounded nucleolus (SN) configuration is essential for embryonic development after meiotic maturation and fertilization. The underlying mechanisms remain unknown. We identify RNA polymerase II (RNAPII) degradation as the key driver of this process. Inhibitors that trigger RNAPII degradation, but not nucleoside-based transcription inhibitors, induce NSN-to-SN transition in oocytes. By establishing miniTrim-Away for nuclear proteins and using segregase and proteasome inhibitors, we demonstrate that RNAPII degradation is necessary and sufficient for NSN-to-SN transition. Further experiments reveal that RNAPII degradation results in a global collapsing force and a local attractive force required for the transition to SN configuration. Finally, embryos derived from NSN oocytes have aberrant RNAPII levels and localization, and are defective in maternal-to-zygotic transition. Our study elucidates the mechanistic framework of oocyte chromatin reorganization and presents a strategy for inducing fully grown oocyte nuclei.

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