对于piRNA放大独立的LINE1转位子沉默,需要Miwi催化
Michael Reuter1, Philipp Berninger, Shinichiro Chuma
1European Molecular Biology Laboratory, 6 Rue Jules Horowitz, BP 181, 38042 Grenoble, France.
Nature
|November 29, 2011
概括
皮维蛋白 (Miwi) 作为切片器,切割转子子子信使RNA以确保男性生育能力. 这一发现揭示了哺乳动物中转子子沉默的第二层,补充了胚胎沉默机制.
科学领域:
- 生殖生物学 生殖生物学
- 分子遗传学 分子遗传学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 皮维相互作用RNAs (piRNAs) 和皮维蛋白 (Mili,Miwi2) 通过男性胚胎生殖系中通过DNA甲基化沉默转体子,这对生育至关重要.
- 第三种Piwi蛋白,Miwi,在产后生殖细胞中发现,具有未知的piRNA功能.
研究的目的:
- 为了研究Piwi蛋白Miwi在小鼠雄性生殖细胞中的功能.
- 确定Miwi是否具有催化活性及其在转子子沉默中的作用.
主要方法:
- 在体外测试测试米维的RNase (切片器) 活性.
- 产生具有催化不活跃的Miwi突变的小鼠,以评估其体内功能.
- 在突变生殖细胞中分析转子子体转录水平.
主要成果:
- 米维作为一个小RNA引导的RNase (切片器) 功能,需要广泛的互补性来实现目标裂解.
- 米维的催化活动中断导致男性不孕症和LINE1逆转移素转录的增加.
- 证据表明,Miwi直接切割转子子信使RNA,支持无需piRNA放大而依赖切片器的沉默机制.
结论:
- 米维在出生后男性生殖细胞中对转录后的转子子沉默起着至关重要的作用.
- 皮维蛋白对哺乳动物的转体子沉默采用双重策略:胚胎中的转录和出生后的后转录.
- 米维的切片活动解释了重复衍生的piRNAs的持久性,并提供了加强转子子沉默的机制.
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