Structural Insight into the Mechanism of Double-Stranded RNA Processing by Ribonuclease III

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.11.034 Byline: Jianhua Gan (1), Joseph E. Tropea (1), Brian P. Austin (1), Donald L. Court (1), David S. Waugh (1), Xinhua Ji (1) Abstract: Members of the ribonuclease III (RNase III) family are double-stranded RNA (dsRNA) specific endoribonucleases characterized by a signature motif in their active centers and a two-base 3' overhang in their products. While Dicer, which produces small interfering RNAs, is currently the focus of intense interest, the structurally simpler bacterial RNase III serves as a paradigm for the entire family. Here, we present the crystal structure of an RNase III-product complex, the first catalytic complex observed for the family. A 7 residue linker within the protein facilitates induced fit in protein-RNA recognition. A pattern of protein-RNA interactions, defined by four RNA binding motifs in RNase III and three protein-interacting boxes in dsRNA, is responsible for substrate specificity, while conserved amino acid residues and divalent cations are responsible for scissile-bond cleavage. The structure reveals a wealth of information about the mechanism of RNA hydrolysis that can be extrapolated to other RNase III family members. Author Affiliation: (1) Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA Article History: Received 17 August 2005; Revised 5 October 2005; Accepted 10 November 2005 Article Note: (miscellaneous) Published: January 26, 2006