R2D2, a Bridge Between the Initiation and Effector Steps of the Drosophila RNAi Pathway

@article{Liu2003R2D2AB,
  title={R2D2, a Bridge Between the Initiation and Effector Steps of the Drosophila RNAi Pathway},
  author={Qinghua Liu and Tim A. Rand and Savitha Kalidas and Fenghe Du and Hyun-eui Kim and Dean P Smith and Xiaodong Wang},
  journal={Science},
  year={2003},
  volume={301},
  pages={1921 - 1925}
}
The RNA interference (RNAi) pathway is initiated by processing long double-stranded RNA into small interfering RNA (siRNA). The siRNA-generating enzyme was purified from Drosophila S2cells and consists of two stoichiometric subunits: Dicer-2(DCR-2) and a previously unknown protein that we named R2D2. R2D2 is homologous to the Caenorhabditis elegans RNAi protein RDE-4. Association with R2D2 does not affect the enzymatic activity of DCR-2. Rather, the DCR-2/R2D2 complex, but not DCR-2 alone… Expand

Paper Mentions

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TLDR
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It is concluded that R2D2 functions beyond its role in RNA interference to include ovarian development in Drosophila and functions in the ovary, specifically in the somatic tissues giving rise to the stalk and other follicle cells critical for establishing the cellular architecture of the oocyte. Expand
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R2D2 and loqs mutants show impaired silencing triggered by injection of exogenous ds RNA or by artificial and natural expression of endogenous dsRNA, and it is shown that these dsRBPs function sequentially and nonredundantly in collaboration with Dcr-2. Expand
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TLDR
It is demonstrated in vivo that efficient removal of the passenger strand from RISC requires the cleavage activity of Ago2, and a new intermediate complex is identified in the RISC assembly pathway, pre-RISC, in which Ago2 is stably bound to double-stranded siRNA. Expand
Functional analysis of dicer-2 missense mutations in the siRNA pathway of Drosophila.
TLDR
It is found that the carboxyl-terminal region of R2D2 is essential for Dicer-2 binding, and further insight is provided into the structure-function relationship of Dicer, which plays a critical role in the siRNA pathway. Expand
C3PO, an Endoribonuclease That Promotes RNAi by Facilitating RISC Activation
TLDR
An in vitro RNAi reconstitution system is established and C3PO is identified as a key activator of the core RNAi machinery, a complex of Translin and Trax. Expand
A Protein Sensor for siRNA Asymmetry
TLDR
In Drosophila, R2D2 is both a protein sensor for siRNA thermodynamic asymmetry and a licensing factor for entry of authentic siRNAs into the RNAi pathway. Expand
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