Argonaute2 is the catalytic engine of mammalian RNAi
Argonaute2 is the catalytic engine of mammalian RNAi
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DOI：
10.1126/science.1102513
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发表时间：
2004-09-03
期刊：
影响因子：
56.9
通讯作者：
Hannon, GJ
中科院分区：
文献类型：
--
作者：
Liu, JD;Carmell, MA;Hannon, GJ
通过RNA干扰（RNAi）的基因沉默是由RISC（RNA诱导的沉默复合物）进行的。RISC包含两个特征组分，小干扰RNA（siRNA）和Argonaute家族蛋白。在这里，我们表明，多种Argonaute蛋白存在于哺乳动物中的生物学和生化不同，与一个单一的哺乳动物家族成员，Argonaute 2，负责信使RNA切割活性。这种蛋白质对小鼠发育至关重要，而Argonaute2的细胞无法对siRNA产生实验性反应。Argonaute2内一个隐蔽核糖核酸酶H结构域内的突变，通过与古细菌结构的比较鉴定。Argonaute蛋白，ARGRISC。因此，我们的证据支持一个模型，其中Argonaute为RISC贡献了“Slicer”活性，为RNAi提供了催化引擎。
Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells tacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal. Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi.