Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III.
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.
Gan
Jianhua
J
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Tropea
Joseph E
JE
Austin
Brian P
BP
Court
Donald L
DL
Waugh
David S
DS
Ji
Xinhua
X
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000378:metabolism*; D043244:Ribonuclease III / Q000737:chemistry* / Q000502:physiology*; D016415:Sequence Alignment; D013379:Substrate Specificity
D046911:Macromolecular Substances; D012330:RNA, Double-Stranded; D043244:Ribonuclease III