The mechanism of RNase III action: How Dicer dices

Members of the Ribonuclease Ill (RNase 111) family are double-stranded (ds) RNA-specific endoribonucleases, characterized by a signature motif in their active centers and a 2-nucleotide (nt) 3' overhang in their products. Dicer functions as a dsRNA-processing enzyme, producing small interfering RNA (siRNA) of approx. 24 nt in length (approx. 20-basepair RNA duplex with a 2-nt 3' overhang on each end). Bacterial RNase Ill functions not only as a processing enzyme, but also as a binding protein that binds dsRNA without cleaving it. As a processing enzyme it produces siRNA-like RNA of approx. 13 nt in length (approx. 9-basepair duplex with a 2-nt 3' overhang on each end) as well as various types of mature RNA. Dicer is structurally most complicated member of the family, bacterial RNase Ill is comparatively much simpler. One structure is known for Dicer in its RNA-free form (MacRae, Zhou, Li, Repic, Brooks, Cande, Adams, and Doudna, Science 311:195-198); many structures are available for bacterial RNase III, including the first catalytic complex of the entire family (Gan, Tropea, Austin, Court, Waugh, and Ji, Cell 124:355-366). In light of the structural and biochemical information on the RNase III proteins and the structure of a non-Dicer PAZ (Piwi Argonaute Zwille) domain in complex with a 7-basepair RNA duplex with a 2-nt 3' overhang on each end (Ma, Ye, and Patel, Nature 429:318-322), the structure and function of Dicer is being elucidated.

See More