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Science 13 January 2006:
Vol. 311. no. 5758, pp. 195 - 198
DOI: 10.1126/science.1121638
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Research Articles

Structural Basis for Double-Stranded RNA Processing by Dicer

Ian J. MacRae,1,3 Kaihong Zhou,1,3 Fei Li,1 Adrian Repic,1 Angela N. Brooks,1 W. Zacheus Cande,1 Paul D. Adams,4 Jennifer A. Doudna1,2,3,4*

The specialized ribonuclease Dicer initiates RNA interference by cleaving double-stranded RNA (dsRNA) substrates into small fragments about 25 nucleotides in length. In the crystal structure of an intact Dicer enzyme, the PAZ domain, a module that binds the end of dsRNA, is separated from the two catalytic ribonuclease III (RNase III) domains by a flat, positively charged surface. The 65 angstrom distance between the PAZ and RNase III domains matches the length spanned by 25 base pairs of RNA. Thus, Dicer itself is a molecular ruler that recognizes dsRNA and cleaves a specified distance from the helical end.

1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
2 Department of Chemistry, University of California, Berkeley, CA 94720, USA.
3 Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
4 Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

* To whom correspondence should be addressed: E-mail: doudna{at}berkeley.edu

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