一种由逆转移素驱动的Dicer异型指导小鼠卵细胞内源性小干扰RNA的产生
Matyas Flemr1, Radek Malik, Vedran Franke
1Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
Cell
|November 12, 2013
概括
在小鼠卵细胞中,一种新的Dicer异型 (Dicer(O)) 驱动小RNA生物发生,这对女性生育至关重要. 这种异构形态是
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- 在哺乳动物中,Dicer对于微RNA (miRNA) 和RNA干扰 (RNAi) 途径中的小RNA生物发生是必不可少的.
- 内源RNAi在小鼠卵细胞中高度活跃,但不是体细胞,这表明有一个专门的机制.
研究的目的:
- 在小鼠中研究卵细胞特异性RNAi活性的分子基础.
- 描述一种新型的Dicer异型,该异型对女性生殖系内源性RNAi负责.
主要方法:
- 在卵细胞和体细胞中对Dicer异型的比较分析.
- 在双链RNA (dsRNA) 基质上Dicer(O) 活性的功能性表征.
- 对驱动DicerO表达的MT-C逆转移素促进体的遗传分析.
主要成果:
- 鉴定了一种卵细胞特异的Dicer异型 (Dicer(O)) 缺乏N端酶域,具有比体性Dicer (Dicer(S)) 更高的裂解活性.
- 迪克 (Dicer) 有效地将长dRNA加工成小RNA,与迪克 (Dicer) 不同.
- 驱动Dicer(O) 表达的内基MT-C逆转移素促进体的删除导致Dicer(O) 的丧失,女性不育,介质缺陷和增加内分泌siRNA标.
结论:
- 卵细胞特异的Dicer(O) 异型是小鼠雌性生殖系内源性RNAi的主要驱动因素.
- 在卵细胞发育和保持基因组完整性方面,Dicer (O) 起着至关重要的作用.
- 这种替代的Dicer异型突出了RNA沉默途径的进化可塑性.
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