Jinek Martin, Doudna Jennifer A
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Nature. 2009 Jan 22;457(7228):405-12. doi: 10.1038/nature07755.
In eukaryotes, small non-coding RNAs regulate gene expression, helping to control cellular metabolism, growth and differentiation, to maintain genome integrity, and to combat viruses and mobile genetic elements. These pathways involve two specialized ribonucleases that control the production and function of small regulatory RNAs. The enzyme Dicer cleaves double-stranded RNA precursors, generating short interfering RNAs and microRNAs in the cytoplasm. These small RNAs are transferred to Argonaute proteins, which guide the sequence-specific silencing of messenger RNAs that contain complementary sequences by either enzymatically cleaving the mRNA or repressing its translation. The molecular structures of Dicer and the Argonaute proteins, free and bound to small RNAs, have offered exciting insights into the molecular mechanisms that are central to RNA silencing pathways.
在真核生物中,小型非编码RNA调节基因表达,有助于控制细胞代谢、生长和分化,维持基因组完整性,并对抗病毒和移动遗传元件。这些途径涉及两种专门的核糖核酸酶,它们控制小型调节RNA的产生和功能。Dicer酶切割双链RNA前体,在细胞质中产生短干扰RNA和微小RNA。这些小RNA被转移到AGO蛋白上,AGO蛋白通过酶切mRNA或抑制其翻译来引导对含有互补序列的信使RNA进行序列特异性沉默。Dicer和AGO蛋白的分子结构,无论是游离状态还是与小RNA结合的状态,都为深入了解RNA沉默途径的核心分子机制提供了令人兴奋的见解。