Structure of Dicer and Mechanistic Implications for RNAi

I. J. MacRae, Fei Li, K. Zhou, W. Z. Cande, J. A. Doudna

Research output: Contribution to journalArticle

Abstract

Dicer is a specialized ribonuclease that processes double-stranded RNA (dsRNA) into small RNA fragments about 25 nucleotides in length during the initiation phase of RNA interference (RNAi). We previously determined the crystal structure of a Dicer enzyme from the diplomonad Giardia intestinalis and proposed a structural model for dsRNA processing. Here, we provide evidence that Dicer is composed of three structurally rigid regions connected by flexible hinges and propose that conformational flexibility facilitates dsRNA binding and processing. We also examine the role of the accessory domains found in Dicers of higher eukaryotes but absent in Giardia Dicer. Finally, we combine the structure of Dicer with published biochemical data to propose a model for the architecture of the RNA-induced silencing complex (RISC)-loading complex.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalCold Spring Harbor Symposia on Quantitative Biology
Volume71
DOIs
StatePublished - 2006

Fingerprint

Double-Stranded RNA
double-stranded RNA
RNA Interference
RNA interference
RNA
Diplomonadida
RNA-Induced Silencing Complex
Ribonuclease III
Giardia
Giardia lamblia
ribonucleases
Structural Models
Accessories
Hinges
Ribonucleases
Processing
crystal structure
Eukaryota
eukaryotic cells
Nucleotides

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Biochemistry
  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Structure of Dicer and Mechanistic Implications for RNAi. / MacRae, I. J.; Li, Fei; Zhou, K.; Cande, W. Z.; Doudna, J. A.

In: Cold Spring Harbor Symposia on Quantitative Biology, Vol. 71, 2006, p. 73-80.

Research output: Contribution to journalArticle

MacRae, I. J. ; Li, Fei ; Zhou, K. ; Cande, W. Z. ; Doudna, J. A. / Structure of Dicer and Mechanistic Implications for RNAi. In: Cold Spring Harbor Symposia on Quantitative Biology. 2006 ; Vol. 71. pp. 73-80.
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