Dicer - A Molecular Ruler

Structural Basis for Double-Stranded RNA Processing by Dicer

Ian J. MacRae, Kaihong Zhou, Fei Li, Adrian Repic, Angela N. Brooks, W. Zacheus Cande, Paul D. Adams, Jennifer A. Doudna.

Science, 2006, 311, 195-198.

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Carl D. Novina and Phillip A. Sharp; Nature 430, 161-164 (2004)

Short RNA’s in Gene Silencing

Carl D. Novina and Phillip A. Sharp; Nature 430, 161-164 (2004)

siRNA pathway

RNAi pathways

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Carl D. Novina and Phillip A. Sharp; Nature 430, 161-164 (2004)

miRNA pathway

RNAi pathways

Classes of RNase

• RNase A - ssRNA cleavage

• RNase P - Ribozyme - tRNA modulation

• RNase H - specific for DNA/RNA hybrid

• RNase II - Exonuclease

• RNase III - specific for dsRNA

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Acid-Base mechanism of ribonuclease A

Michelle A. Carmell, Gregory J. Hannon Nature Structural & Molecular Biology, 11, 214 - 218 (2004)

Classes of RNase III

Dicer Activity in Giardia intestinalis

= PAZ domain

= RNase III domains

- N-Terminal DExD/H Helicase

- C-Terminal double-stranded RNA binding domain (dsRBD)

- Extended inter-domain regions

Fig. 1. Giardia encodes an active Dicer enzyme.

Fig. 2. Crystal structure of Giardia Dicer.

Fig. 3. Structural features of the Dicer PAZ domain.

Michelle A. Carmell, Gregory J. Hannon Nature Structural & Molecular Biology, 11, 214 - 218 (2004)

Fig. 4. A model for dsRNA processing by Dicer.

Fig. 5. Giardia Dicer supports RNAi in vivo.