Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes
Summary: 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 m...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723012597 |
| _version_ | 1797660131575463936 |
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| author | Di Wu Jurrien Dean |
| author_facet | Di Wu Jurrien Dean |
| author_sort | Di Wu |
| collection | DOAJ |
| description | Summary: 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 (Dis3cKO) 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. Dis3cKO 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. |
| first_indexed | 2024-03-11T18:25:21Z |
| format | Article |
| id | doaj.art-b9b1672d5a3c436e8b1c802dbc4498fc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T18:25:21Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b9b1672d5a3c436e8b1c802dbc4498fc2023-10-14T04:44:34ZengElsevierCell Reports2211-12472023-10-014210113247Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytesDi Wu0Jurrien Dean1Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authorLaboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authorSummary: 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 (Dis3cKO) 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. Dis3cKO 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.http://www.sciencedirect.com/science/article/pii/S2211124723012597CP: Molecular biology |
| spellingShingle | Di Wu Jurrien Dean Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes Cell Reports CP: Molecular biology |
| title | Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes |
| title_full | Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes |
| title_fullStr | Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes |
| title_full_unstemmed | Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes |
| title_short | Reduced female fertility due to sequestration of RNA Pol II by pervasive transcription in exosome RNase-depleted oocytes |
| title_sort | reduced female fertility due to sequestration of rna pol ii by pervasive transcription in exosome rnase depleted oocytes |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723012597 |
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