PABPN1L是必要的母体的mRNA降解后复杂化恢复变质
Chihiro Emori1, Mayo Kodani1,2, Ferheen Abbasi1,3
1Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
The Journal of reproduction and development
|December 6, 2023
概括
聚A结合蛋白核1-like (PABPN1L) 对于雌性小鼠的生育能力至关重要. 由于卵细胞成熟期间的mRNA降解有缺陷,其缺乏会导致不孕症,从而损害胚胎发育.
科学领域:
- 生殖生物学 生殖生物学
- 分子遗传学 分子遗传学
- 细胞生物学 细胞生物学
背景情况:
- 多A结合蛋白 (PABPs) 在体细胞中对mRNA调节至关重要.
- 包括PABPN1L在内的PABP在卵细胞中的特定作用,由于卵细胞独特的mRNA代谢,在很大程度上仍未被描述.
研究的目的:
- 研究PABPN1L在小鼠卵细胞中的功能及其对女性生育能力的影响.
- 阐明PABPN1L在胚胎发育中的作用背后的分子机制.
主要方法:
- 通过使用CRISPR/Cas9技术,生成了Pabpn1l淘汰赛 (KO) 鼠标.
- 交配测试用于评估KO小鼠的雌性生育能力.
- RNA测序 (RNA-seq) 用于分析卵细胞中的mRNA配置文件.
- 在KO卵细胞中Pabpn1lmRNA的外源表达,以评估救援效应.
主要成果:
- 在Pabpn1l KO中,雌性小鼠表现出不孕不育,胚胎无法超过4细胞阶段的发育.
- RNA-seq分析揭示了KO-MII卵细胞中的持续异常mRNA,表明在胚芽囊泡 (GV) 到MII过渡期间mRNA降解受损.
- 对外表达Pabpn1lmRNA拯救了KO-GV卵细胞中的胚胎发育缺陷.
结论:
- PABPN1L对于胚胎发育至关重要,因此在部分情况下对于小鼠雌性生育是不可或缺的.
- PABPN1L的必要性与其在GV到MII卵细胞成熟过程中促进适当的mRNA降解的作用有关.
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