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

Abstract

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.

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Figure 1: Structure of RNaseIII-family enzymes.
Figure 2: Modular architecture of Argonaute proteins.
Figure 3: Recognition of the termini of small RNAs by the PAZ and MID domains of Argonaute proteins.
Figure 4: Mechanism of guide- and target-strand recognition by Argonaute proteins.

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Acknowledgements

We are grateful to D. Patel for communicating results in advance of publication. We also thank members of the Doudna laboratory for discussions and critical reading of the manuscript. Research in the Doudna laboratory is supported by the Howard Hughes Medical Institute and the National Institutes of Health. M.J. was supported by the European Molecular Biology Organization and is now a postdoctoral fellow of the Human Frontier Science Program.

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Jinek, M., Doudna, J. A three-dimensional view of the molecular machinery of RNA interference. Nature 457, 405–412 (2009). https://doi.org/10.1038/nature07755

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