| First Author | Wu D | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 10 | Pages | 113247 |
| PubMed ID | 37831603 | Mgi Jnum | J:342162 |
| Mgi Id | MGI:7546694 | Doi | 10.1016/j.celrep.2023.113247 |
| Citation | Wu D, et al. (2023) Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes. Cell Rep 42(10):113247 |
| abstractText | Perturbing the transcriptome of mammalian oocytes results in meiotic failure. We previously reported that RNA-exosome-associated RNase, EXOSC10, degrades unwanted protein-coding RNA and processes ribosomal RNA to ensure proper oocyte maturation. Here, we establish oocyte-specific knockout mice of another RNA-exosome-associated RNase, DIS3. Mutant females (Dis3(cKO)) exhibit significantly reduced fertility because oocytes arrest after the growth phase. Single-oocyte RNA sequencing (RNA-seq) and CUT&Tag analyses show that DIS3 degrades intergenic RNA and mediates transcription silencing that is essential for chromatin condensation and resumption of meiosis. Dis3(cKO) oocytes exhibit elevated H3K27me3 in a pre-defined manner due to insufficient demethylation. During oocyte growth, EXOSC10 functions with DIS3 to degrade intergenic RNA. Double-knockout oocytes have earlier growth defects and more accumulated transcripts. We conclude that RNA exosomes synergistically degrade unwanted RNA and mediate transcription termination to ensure transcriptome integrity during oocyte development. |
