Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Cold Spring Harb Perspect Biol. 2011 Oct 1;3(10):a003772. doi: 10.1101/cshperspect.a003772.
RNAi has existed at least since the divergence of prokaryotes and eukaryotes. This collection of pathways responds to a diversity of "abberant" RNAs and generally silences or eliminates genes sharing sequence content with the silencing trigger. In the canonical pathway, double-stranded RNAs are processed into small RNAs, which guide effector complexes to their targets by complementary base pairing. Many alternative routes from silencing trigger to small RNA are continuously being uncovered. Though the triggers of the pathway and the mechanisms of small RNA production are many, all RNAi-related mechanisms share Argonaute proteins as the heart of their effector complexes. These can act as self-contained silencing machines, binding directly to small RNAs, carrying out homology-based target recognition, and in some cases cleaving targets using an endogenous nuclease domain. Here, we discuss the diversity of Argonaute proteins from a structural and functional perspective.
RNAi 至少存在于原核生物和真核生物分化之后。这一系列途径对各种“异常”RNA 做出反应,通常会使与沉默触发物具有序列内容的基因沉默或消除。在经典途径中,双链 RNA 被加工成小 RNA,小 RNA 通过互补碱基配对引导效应因子复合物到达其靶标。不断有新的从沉默触发物到小 RNA 的替代途径被发现。尽管该途径的触发物和小 RNA 产生的机制多种多样,但所有与 RNAi 相关的机制都将 Argonaute 蛋白作为其效应因子复合物的核心。Argonaute 蛋白可以作为独立的沉默机器,直接与小 RNA 结合,进行基于同源性的靶标识别,在某些情况下还可以利用内源性核酸内切酶结构域切割靶标。在这里,我们从结构和功能的角度讨论 Argonaute 蛋白的多样性。