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ToolsDo, Dang Vinh, Strauss, Bernhard, Cukuroglu, Engin, Macaulay, Iain, Wee, Keng Boon, Hu, Tim Xiaoming, Igor, Ruiz De Los Mozos, Lee, Caroline, Harrison, Andrew, Butler, Richard, Dietmann, Sabine, Jernej, Ule, Marioni, John, Smith, Christopher W. J., Göke, Jonathan and Surani, M. Azim (2018) SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements. Cell Discovery, 4 (1). ISSN 2056-5968
Full text not available from this repository. (Request a copy)Abstract
The RNA-binding protein SRSF3 (also known as SRp20) has critical roles in the regulation of pre-mRNA splicing. Zygotic knockout of Srsf3 results in embryo arrest at the blastocyst stage. However, SRSF3 is also present in oocytes, suggesting that it might be critical as a maternally inherited factor. Here we identify SRSF3 as an essential regulator of alternative splicing and of transposable elements to maintain transcriptome integrity in mouse oocyte. Using 3D time-lapse confocal live imaging, we show that conditional deletion of Srsf3 in fully grown germinal vesicle oocytes substantially compromises the capacity of germinal vesicle breakdown (GVBD), and consequently entry into meiosis. By combining single cell RNA-seq, and oocyte micromanipulation with steric blocking antisense oligonucleotides and RNAse-H inducing gapmers, we found that the GVBD defect in mutant oocytes is due to both aberrant alternative splicing and derepression of B2 SINE transposable elements. Together, our study highlights how control of transcriptional identity of the maternal transcriptome by the RNA-binding protein SRSF3 is essential to the development of fertilized-competent oocytes.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: We thank Dr. Peter J. Nielsen from the Max Planck Institute for Immunology and Epigenetics for kindly providing the Srsf3flox/flox mice, Dr. Bill Mansfield and Charles-Etienne Dumeau for helping mouse embryo work, Dr. Melina Schuh and Dr. Dean Cliff for their advice in live imaging, Dr. Ernesto Guccione and Dr. Cheryl Koh for their advice on splicing analysis. This research was supported by Gurdon Institute core grants from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492), and a grant from the Wellcome Trust to M.A.S. (WT096738). Publisher Copyright: © 2018 The Author(s). |
| Uncontrolled Keywords: | biochemistry,molecular biology,genetics,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1303 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 01 Nov 2022 16:30 |
| Last Modified: | 02 Nov 2022 15:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/89490 |
| DOI: | 10.1038/s41421-018-0032-3 |
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