Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Science Signaling - Call for Papers

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

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

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Conifers have a unique small RNA silencing signature.
E. V. Dolgosheina, R. D. Morin, G. Aksay, S. C. Sahinalp, V. Magrini, E. R. Mardis, J. Mattsson, and P. J. Unrau (2008)
RNA 14, 1508-1515
   Abstract »    Full Text »    PDF »
From the Cover: The RNA-binding proteins HYL1 and SE promote accurate in vitro processing of pri-miRNA by DCL1.
Z. Dong, M.-H. Han, and N. Fedoroff (2008)
PNAS 105, 9970-9975
   Abstract »    Full Text »    PDF »
The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members.
T. A. Farazi, S. A. Juranek, and T. Tuschl (2008)
Development 135, 1201-1214
   Abstract »    Full Text »    PDF »
Structural and biochemical insights into the dicing mechanism of mouse Dicer: A conserved lysine is critical for dsRNA cleavage.
Z. Du, J. K. Lee, R. Tjhen, R. M. Stroud, and T. L. James (2008)
PNAS 105, 2391-2396
   Abstract »    Full Text »    PDF »
P68 RNA Helicase Unwinds the Human let-7 MicroRNA Precursor Duplex and Is Required for let-7-directed Silencing of Gene Expression.
D. W. Salzman, J. Shubert-Coleman, and H. Furneaux (2007)
J. Biol. Chem. 282, 32773-32779
   Abstract »    Full Text »    PDF »
Functional Anatomy of the Drosophila MicroRNA-generating Enzyme.
X. Ye, Z. Paroo, and Q. Liu (2007)
J. Biol. Chem. 282, 28373-28378
   Abstract »    Full Text »    PDF »
Combined experimental and computational approach to identify non-protein-coding RNAs in the deep-branching eukaryote Giardia intestinalis.
X. Chen, T. S. Rozhdestvensky, L. J. Collins, J. Schmitz, and D. Penny (2007)
Nucleic Acids Res. 35, 4619-4628
   Abstract »    Full Text »    PDF »
Human TRBP and PACT Directly Interact with Each Other and Associate with Dicer to Facilitate the Production of Small Interfering RNA.
K. H. Kok, M.-H. J. Ng, Y.-P. Ching, and D.-Y. Jin (2007)
J. Biol. Chem. 282, 17649-17657
   Abstract »    Full Text »    PDF »
Structure of Aquifex aeolicus Argonaute Highlights Conformational Flexibility of the PAZ Domain as a Potential Regulator of RNA-induced Silencing Complex Function.
U. J. Rashid, D. Paterok, A. Koglin, H. Gohlke, J. Piehler, and J. C.-H. Chen (2007)
J. Biol. Chem. 282, 13824-13832
   Abstract »    Full Text »    PDF »
RNA stem-loops: To be or not to be cleaved by RNAse III.
W. Ritchie, M. Legendre, and D. Gautheret (2007)
RNA 13, 457-462
   Abstract »    Full Text »    PDF »
Genome-Wide Analysis of the RNA-DEPENDENT RNA POLYMERASE6/DICER-LIKE4 Pathway in Arabidopsis Reveals Dependency on miRNA- and tasiRNA-Directed Targeting.
M. D. Howell, N. Fahlgren, E. J. Chapman, J. S. Cumbie, C. M. Sullivan, S. A. Givan, K. D. Kasschau, and J. C. Carrington (2007)
PLANT CELL 19, 926-942
   Abstract »    Full Text »    PDF »
Specific residues at every third position of siRNA shape its efficient RNAi activity.
T. Katoh and T. Suzuki (2007)
Nucleic Acids Res. 35, e27
   Abstract »    Full Text »    PDF »
Selenium derivatization of nucleic acids for crystallography.
J. Jiang, J. Sheng, N. Carrasco, and Z. Huang (2007)
Nucleic Acids Res. 35, 477-485
   Abstract »    Full Text »    PDF »
An unusual Dicer-like1 protein fuels the RNA interference pathway in Trypanosoma brucei.
H. Shi, C. Tschudi, and E. Ullu (2006)
RNA 12, 2063-2072
   Abstract »    Full Text »    PDF »
DUF283 domain of Dicer proteins has a double-stranded RNA-binding fold.
M. Dlakic (2006)
Bioinformatics 22, 2711-2714
   Abstract »    Full Text »    PDF »
Characterization of RNA sequence determinants and antideterminants of processing reactivity for a minimal substrate of Escherichia coli ribonuclease III.
A. V. Pertzev and A. W. Nicholson (2006)
Nucleic Acids Res. 34, 3708-3721
   Abstract »    Full Text »    PDF »
A novel class of small RNAs in mouse spermatogenic cells.
S. T. Grivna, E. Beyret, Z. Wang, and H. Lin (2006)
Genes & Dev. 20, 1709-1714
   Abstract »    Full Text »    PDF »
Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction.
C.-I. An, V. B. Trinh, and Y. Yokobayashi (2006)
RNA 12, 710-716
   Abstract »    Full Text »    PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)