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SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements

Published version
Peer-reviewed

Type

Article

Change log

Authors

Dang Do, Vinh 
Strauss, Bernhard 
Cukuroglu, Engin 
Macaulay, Iain 
Boon Wee, Keng 

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.

Description

Keywords

Generic Health Relevance

Journal Title

Cell Discovery

Conference Name

Journal ISSN

2056-5968
2056-5968

Volume Title

4

Publisher

Springer Nature
Sponsorship
Wellcome Trust (209475/Z/17/Z)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (096738/Z/11/Z)
Cancer Research Uk (None)
Cancer Research UK (22231)