SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements
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Authors
Dang Do, Vinh
Strauss, Bernhard
Cukuroglu, Engin
Macaulay, Iain
Boon Wee, Keng
Xiamoming, Tim
Ruiz De Los Mozos, Igor
Lee, Caroline
Dietmann, Sabine
Jernej, Ule
Goke, Jonathan
Publication Date
2018Journal Title
Cell Discovery
ISSN
2056-5968
Publisher
Springer Nature
Volume
4
Number
33
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Dang Do, V., Strauss, B., Cukuroglu, E., Macaulay, I., Boon Wee, K., Xiamoming, T., Ruiz De Los Mozos, I., et al. (2018). SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements. Cell Discovery, 4 (33) https://doi.org/10.1038/s41421-018-0032-3
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 de-repression 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.
Sponsorship
Wellcome Trust (209475/Z/17/Z)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (096738/Z/11/Z)
Cancer Research Uk (None)
Identifiers
External DOI: https://doi.org/10.1038/s41421-018-0032-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279324
Rights
Attribution 4.0 International (CC BY 4.0), Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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