A three-dimensional view of the molecular machinery of RNA interference

被引:536
作者
Jinek, Martin [1 ]
Doudna, Jennifer A. [1 ,2 ,3 ,4 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
PIWI-INTERACTING RNAS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; HUMAN DICER; MICRORNA MATURATION; ARGONAUTE COMPLEXES; SILENCING COMPLEX; PASSENGER-STRAND; GUIDE-STRAND; PAZ DOMAIN;
D O I
10.1038/nature07755
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:405 / 412
页数:8
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