阿尔戈瑙特
Piwi相互作用RNA
核糖核酸
生物
掷骰子
RNA诱导的转录沉默
拉西尔纳
RNA沉默
非编码RNA
RNA诱导沉默复合物
RNA依赖性RNA聚合酶
小核RNA
RNA干扰
分子生物学
细胞生物学
生物化学
遗传学
基因
作者
Jinbiao Ma,Yunbin Yuan,Gunter Meister,Yi Pei,Thomas Tuschl,Dinshaw J. Patel
出处
期刊:Nature
[Springer Nature]
日期:2005-03-01
卷期号:434 (7033): 666-670
被引量:580
摘要
RNA interference (RNAi) is a conserved sequence-specific gene regulatory mechanism mediated by the RNA-induced silencing complex (RISC), which is composed of a single-stranded guide RNA and an Argonaute protein. The PIWI domain, a highly conserved motif within Argonaute, has been shown to adopt an RNase H fold critical for the endonuclease cleavage activity of RISC. Here we report the crystal structure of Archaeoglobus fulgidus Piwi protein bound to double-stranded RNA, thereby identifying the binding pocket for guide-strand 5'-end recognition and providing insight into guide-strand-mediated messenger RNA target recognition. The phosphorylated 5' end of the guide RNA is anchored within a highly conserved basic pocket, supplemented by the carboxy-terminal carboxylate and a bound divalent cation. The first nucleotide from the 5' end of the guide RNA is unpaired and stacks over a conserved tyrosine residue, whereas successive nucleotides form a four-base-pair RNA duplex. Mutation of the corresponding amino acids that contact the 5' phosphate in human Ago2 resulted in attenuated mRNA cleavage activity. Our structure of the Piwi-RNA complex, and that determined elsewhere, provide direct support for the 5' region of the guide RNA serving as a nucleation site for pairing with target mRNA and for a fixed distance separating the RISC-mediated mRNA cleavage site from the anchored 5' end of the guide RNA.
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