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

The RNA-binding proteinSRSF3 (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 splicingand of transposable elementsto maintain transcriptomeintegrity in mouse oocyte. Using 3D time-lapse confocal live imaging, we show that conditional deletion of Srsf3 in fully grown germinal vesicle oocytessubstantially compromises the capacity of germinal vesicle breakdown (GVBD), and consequently entry into meiosis. By combining single cell RNA-seq, and oocyte micromanipulationwith steric blocking antisense oligonucleotides and RNAse-Hinducing gapmers, we found that the GVBD defect in mutant oocytesis due to both aberrant alternative splicingand derepressionof B2 SINE transposable elements. Together, our study highlights how control of transcriptional identity of the maternal transcriptomeby the RNA-binding proteinSRSF3 is essential to the development of fertilized-competent oocytes.