SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements.
SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements.
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DOI：
10.1038/s41421-018-0032-3
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发表时间：
2018
期刊：
影响因子：
33.5
通讯作者：
Surani MA
中科院分区：
文献类型：
--
作者：
Do DV;Strauss B;Cukuroglu E;Macaulay I;Wee KB;Hu TX;Igor RLM;Lee C;Harrison A;Butler R;Dietmann S;Jernej U;Marioni J;Smith CWJ;Göke J;Surani MA
RNA结合蛋白SRSF 3（也称为SRp 20）在前体mRNA剪接的调节中具有关键作用。Srsf 3的合子敲除导致胚泡阶段的胚胎停滞。然而，SRSF 3也存在于卵母细胞中，这表明它可能是一个重要的母系遗传因子。在这里，我们确定SRSF 3作为一个重要的调节器的选择性剪接和转座因子，以保持转录组的完整性，在小鼠卵母细胞。使用3D延时共聚焦实时成像，我们表明，在完全生长的germinal囊泡卵母细胞中的Srsf 3的条件性缺失实质上损害germinal囊泡分解（GVBD）的能力，并因此进入减数分裂。通过将单细胞RNA-seq和卵母细胞显微操作与空间阻断反义寡核苷酸和RNAse-H诱导gapmer相结合，我们发现突变卵母细胞中的GVBD缺陷是由于异常选择性剪接和B2 SINE转座因子的去阻遏。总之，我们的研究强调了RNA结合蛋白SRSF 3如何控制母体转录组的转录特性对受精卵母细胞的发育至关重要。
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.
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