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

• Published in: Nature Vol. 457; no. 7228; pp. 405 - 412
• Main Authors: Doudna, Jennifer A, Jinek, Martin
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 22.01.2009
• Subjects: Animals; Enzymes; Gene silencing; Genetic regulation; Humans; MicroRNAs - biosynthesis; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular biology; Physiological aspects; Proteins; Ribonuclease III - metabolism; Ribonucleic acid; RNA; RNA Interference - physiology; RNA, Small Interfering - biosynthesis; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA-Induced Silencing Complex - metabolism; United States
• ISSN: 0028-0836; 1476-4687; 1476-4679
• 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.