PLX153032

GSE141190: EXOSC10 sculpts the transcriptome during oocyte growth-to-maturation transition

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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 germinal vesicle breakdown (GVBD, envisioned as nuclear envelope breakdown) 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, sculpts the transcriptome at multiple level 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 in different ways, we document dysregulated transcriptomes, unsuccessfully processed rRNAs 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 mRNAs that encode growth-phase factors and sculpting the transcriptome to support the maturation phase of oogenesis. SOURCE: Di Wu (di.wu2@nih.gov) - LCDB NIH