PT  - JOURNAL ARTICLE
AU  - Di Wu
AU  - Cameron Palmer
AU  - Jurrien Dean
TI  - EXOSC10 mediated RNA degradation sculpts the transcriptome during oocyte growth-to-maturation transition
AID  - 10.1101/663377
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 663377
4099  - http://biorxiv.org/content/early/2019/07/25/663377.short
4100  - http://biorxiv.org/content/early/2019/07/25/663377.full
AB  - Growing mammalian oocytes accumulate substantial amounts of RNA, most of which are degraded during the subsequent maturation stage. The growth-to-maturation transition begins with nuclear envelope breakdown (GVBD) and is critical for oocyte quality. However, the concomitant changes in the transcriptome during GVBD as well as the underlying machinery remained unclear. Here, we report that an RNA exosome-associated RNase, EXOSC10, degrades poly(A) RNA to facilitate the oocyte growth-to-maturation transition. We establish an oocyte-specific knockout of Exosc10 in mice using CRISPR/Cas9 and find female subfertility due to failed GVBD. By performing single oocyte RNA-seq at GV, GVBD and MII stages, we document dysregulated transcriptomes in mutant oocytes, and many up-regulated RNAs that encode proteins important for endomembrane trafficking, meiotic cell cycle and RNA metabolism. EXOSC10-depleted oocytes have impaired endomembrane components including endosome, lysosome, ER and Golgi. In addition, CDK1 fails to be activated possibly due to persistent WEE1 activity, which blocked lamina phosphorylation and disassembly in mutant oocytes. Collectively, we propose that EXOSC10 promotes the growth-to-maturation transition in mouse oocytes by degrading growth-phase factors and sculpting the transcriptome to support the maturation phase of oogenesis.