Distinct Roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA Silencing Pathways

@article{Lee2004DistinctRF,
  title={Distinct Roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA Silencing Pathways},
  author={Young Sik Lee and Kenji S. Nakahara and John W Pham and Kevin Kim and Zhengying He and Erik J. Sontheimer and Richard W. Carthew},
  journal={Cell},
  year={2004},
  volume={117},
  pages={69-81}
}

Figures from this paper

Functional analysis of dicer-2 missense mutations in the siRNA pathway of Drosophila.

Understanding Small RNA Formation in Drosophila Melanogaster: A Dissertation

It is proposed that the Dicer-2 helicase domain uses ATP to generate many siRNAs from a single molecule of dsRNA before dissociating from its substrate, which sheds light onto the function of the helicasedomain in Drosophila Dicers.

The C-terminal dsRNA-binding domain of Drosophila Dicer-2 is crucial for efficient and high-fidelity production of siRNA and loading of siRNA to Argonaute2.

Light is shed on the molecular mechanism by which Dicer-2 produces 21-nt siRNAs with a high efficiency and fidelity for efficient RNA silencing and proposes that CdsRBD binds the proximal body region of a long dsRNA substrate whose 5'-monophosphate end is anchored by the phosphate-binding pocket in the PAZ domain.

Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways.

It is shown that AGO2 is an essential component for siRNA-directed RNA interference (RNAi) response and is required for the unwinding of siRNA duplex and in consequence assembly of si RNA into RISC in Drosophila embryos, and that distinct Argonaute proteins act at different steps of the small RNA silencing mechanism.

Targeting of Dicer-2 and RNA by a Viral RNA Silencing Suppressor in Drosophila Cells

This work shows that the B2 protein from Wuhan nodavirus (WhNV), the counterpart of Flock House virus, suppresses Drosophila melanogaster RNAi by directly interacting with Dicer-2 (Dcr-2) and sequestering double-stranded RNA (dsRNA) and small interfering RNA (siRNA).

Production of small RNAs by mammalian Dicer

The mammalian Dicer is well adapted to produce miRNAs while its ability to support RNAi is limited, and this review discusses key structural features of Dicer and other factors defining Dicer substrate repertoire and biological functions in mammals in comparison with invertebrate models.

Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA production

It is proposed that the 5′-monophosphate of a long dsRNA substrate is anchored by the phosphate-binding pocket in the Dicer-2 PAZ domain and the distance between the pocket and the RNA cleavage active site in the RNaseIII domain corresponds to the 21-nt pitch in the A-form duplex of along ds RNA substrate, resulting in high-fidelity 21-NT siRNA production.

Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila.

A novel dsRNA-binding protein, which is named R3D1-L, that forms a stable complex with Dicer-1 in vitro and in vivo and is required for reproductive development in Drosophila.
...

References

SHOWING 1-10 OF 53 REFERENCES

Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans.

A combination of phenotypic abnormalities and RNA analysis suggests a role for dcr-1 in a regulatory pathway comprised of small temporal RNA (let-7) and its target (e.g., lin-41).

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

It is indicated that R2D2 bridges the initiation and effector steps of the Drosophila RNAi pathway by facilitating siRNA passage from Dicer to RISC.

Role for a bidentate ribonuclease in the initiation step of RNA interference

Dicer is a member of the RNase III family of nucleases that specifically cleave double-stranded RNAs, and is evolutionarily conserved in worms, flies, plants, fungi and mammals, and has a distinctive structure, which includes a helicase domain and dualRNase III motifs.

Ribonuclease activity and RNA binding of recombinant human Dicer

Cl cloning and expression of the 218 kDa human Dicer are reported, and characterization of its ribonuclease activity and dsRNA‐binding properties are described, suggesting that ionic interactions are involved in ds RNA cleavage.

Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing

Dicer-generated siRNAs (d-siRNAs) are effective in silencing transiently transfected reporter genes and endogenous genes, making in vitro dicing a useful, practical alternative for the production of si RNAs.

A microRNA in a Multiple-Turnover RNAi Enzyme Complex

It is shown that, in human cell extracts, the miRNA let-7 naturally enters the RNAi pathway, which suggests that only the degree of complementarity between a miRNA and its RNA target determines its function.
...