Structural basis for double-stranded RNA processing by Dicer.
The specialized ribonuclease Dicer initiates RNA interference by cleaving double-stranded RNA (dsRNA) substrates into small fragments about 25 nucleotides in length. In the crystal structure of an intact Dicer enzyme, the PAZ domain, a module that binds the end of dsRNA, is separated from the two catalytic ribonuclease III (RNase III) domains by a flat, positively charged surface. The 65 angstrom distance between the PAZ and RNase III domains matches the length spanned by 25 base pairs of RNA. Thus, Dicer itself is a molecular ruler that recognizes dsRNA and cleaves a specified distance from the helical end.
Macrae
Ian J
IJ
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Zhou
Kaihong
K
Li
Fei
F
Repic
Adrian
A
Brooks
Angela N
AN
Cande
W Zacheus
WZ
Adams
Paul D
PD
Doudna
Jennifer A
JA
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D016829:Giardia lamblia / Q000201:enzymology; D006801:Humans; D028581:Lanthanoid Series Elements / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism*; D016053:RNA, Protozoan / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000737:chemistry* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics; D013329:Structure-Activity Relationship
D028581:Lanthanoid Series Elements; D012330:RNA, Double-Stranded; D016053:RNA, Protozoan; D011993:Recombinant Fusion Proteins; C523566:Dicer protein, Giardia intestinalis; D043244:Ribonuclease III