RNA Splicing and Alternative Polyadenylation Profile during Sheep Zygotic Genome Activation.

IF 3.1 2区 生物学 Q2 REPRODUCTIVE BIOLOGY
Mingtian Deng, Hua Yang, Ying Chen, Nasser Ghanem, Yingnan Yang, Xiaowei Chen, Zhang JinHao, Feng Wang, Liqin Wang, Yanli Zhang
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Abstract

Zygotic genome activation (ZGA) is a critical biological step in mammalian early embryo development. However, ZGA initiation in sheep and the related sophisticated RNA metabolism remains largely unknown. Here, we observed extensive alterations in gene expression and DNA methylation patterns, along with elevated levels of RNA polymerase II (RNAPII) and its phosphorylation at serine 2 (RNAPII-Ser2P) at the 16-cell stage. Moreover, the embryos were blocked at the 16-cell stage embryo when treated with α-Amanitin, indicating that ZGA is initiated at the 16-cell stage in sheep in vitro fertilized embryos. To uncover the sophisticated RNA metabolism during ZGA, we conducted weighted gene co-expression network analysis and identified 1957 critical maternal genes, including TET3, UHRF1 and KIF2C. Using dapars analysis, we discovered 1058 and 933 lengthened alternative polyadenylation (APA) events during ZGA in sheep and mice. Specifically, genes exhibiting shorten APA were highly expressed at sheep 16-cell stage embryos and mouse 2-cell stage embryos. During ZGA in sheep and mice, 2675 and 1963 genes showed exon skipping, an alternative splicing (AS) events, which is related to RNA binding, translation, gamete generation, and reproduction. Of note, inhibition of AS led to 2-cell block in mice and 8/16-cell block in sheep. Moreover, 5-EU, RNAPII, and RNAPII-Ser2P signal were decreased in AS inhibited 2-cell embryos in mice, suggesting AS might regulate the ZGA process by crosstalk with RNAPII. In conclusion, our data confirmed ZGA initiation at the 16-cell stage embryos, and provides insights into the complex RNA metabolism during ZGA in mammals.

绵羊合子基因组激活过程中的RNA剪接和选择性聚腺苷化谱。
合子基因组激活(Zygotic genome activation, ZGA)是哺乳动物早期胚胎发育的关键生物学步骤。然而,绵羊的ZGA起始和相关的复杂RNA代谢在很大程度上仍然未知。在这里,我们观察到基因表达和DNA甲基化模式的广泛改变,以及RNA聚合酶II (RNAPII)水平的升高及其丝氨酸2磷酸化(RNAPII- ser2p)在16个细胞阶段。α-Amanitin在绵羊体外受精胚胎的16细胞期就阻断了胚胎,表明ZGA在绵羊体外受精胚胎的16细胞期就启动了。为了揭示ZGA过程中复杂的RNA代谢,我们进行了加权基因共表达网络分析,并鉴定了1957个关键母系基因,包括TET3, UHRF1和KIF2C。通过dapars分析,我们在绵羊和小鼠的ZGA中发现了1058和933个延长的选择性多聚腺苷化(APA)事件。具体来说,APA缩短的基因在绵羊16细胞期胚胎和小鼠2细胞期胚胎中高度表达。在绵羊和小鼠的ZGA过程中,2675和1963基因出现外显子跳变,这是一种选择性剪接(AS)事件,与RNA结合、翻译、配子产生和繁殖有关。值得注意的是,抑制AS导致小鼠2细胞阻滞和绵羊8/16细胞阻滞。此外,AS抑制小鼠2细胞胚胎中5-EU、RNAPII和RNAPII- ser2p信号减少,提示AS可能通过与RNAPII的串扰调控ZGA过程。总之,我们的数据证实了ZGA在16细胞期胚胎中启动,并为哺乳动物ZGA过程中复杂的RNA代谢提供了见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biology of Reproduction
Biology of Reproduction 生物-生殖生物学
CiteScore
6.30
自引率
5.60%
发文量
214
审稿时长
1 months
期刊介绍: Biology of Reproduction (BOR) is the official journal of the Society for the Study of Reproduction and publishes original research on a broad range of topics in the field of reproductive biology, as well as reviews on topics of current importance or controversy. BOR is consistently one of the most highly cited journals publishing original research in the field of reproductive biology.
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