米利的内核酶活动推动了piRNA放大,使LINE1元素保持沉默
Serena De Fazio1, Nenad Bartonicek, Monica Di Giacomo
1European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy.
Nature
|October 25, 2011
概括
像Mili这样的Piwi蛋白质对于放大piRNAs (Piwi相互作用RNAs) 来使LINE1转位子沉默至关重要. 破坏民兵的行为
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:
- 皮维蛋白和piRNAs对于转子子沉默至关重要,特别是在生殖线发育期间.
- 米利和Miwi2是参与LINE1和内A粒子 (IAP) 转位子表观遗传沉默的小鼠Piwi蛋白.
- 皮维蛋白在piRNA生物发生和转子子子控制中的内核酶活性的确切作用尚不清楚.
研究的目的:
- 调查Piwi催化内核酶活性在piRNA生物发生和转子子沉默中的功能意义.
- 通过分析催化不活性突变体,阐明米利和Miwi2在这些过程中的特定作用.
- 确定Piwi内核酶活性对LINE1和IAP转体子沉默和男性生育能力的贡献.
主要方法:
- 在Mili和Miwi2的催化DDH三元组中产生点突变的小鼠,产生Mili ((DAH) 和Miwi2 ((DAH) 等位基因.
- 从突变小鼠的淋巴细胞中分析piRNA种群和转子子沉默.
- 在Mili (DAH) 和Miwi (DAH) 同卵性小鼠中评估生育能力和精子生成.
主要成果:
- 毫米 ((DAH) 突变破坏了piRNA放大,导致Miwi2复合体中的piRNAs减少和LINE1沉默受损.
- 毫米介导的piRNA放大对于LINE1沉默是必不可少的,但对于IAP沉默则不是.
- 同性卵性Miwi2 ((DAH) 鼠是肥沃的,具有正常的转位子沉默和二次piRNA生物发生,表明Mili在放大中的主要作用.
- 在米利的DAH小鼠中,有缺陷的piRNA通路导致了精子生成失败和不育.
结论:
- 内米二次piRNA生物发生驱动piRNA放大,这是LINE1沉默不可或缺的.
- 米利的内核酶活性对piRNA放大和LINE1沉默至关重要,影响男性生育能力.
- 在男性生殖系中,Miwi2的内核酶活性对于piRNA放大或LINE1沉默并不重要.
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