Structural and functional insights into humanTudor-SN, a key component linking
 RNA interference and editing

Chia-Lung Li1, Wei-Zen Yang1, Yi-Ping Chen1 and Hanna S. Yuan1,2,*
1Institute of Molecular Biology, Academia Sinica and 2Graduate Institute of Biochemistry and Molecular Biology,College of Medicine, National Taiwan University, Taipei, Taiwan, ROC Received January 29, 2008; Revised April 7, 2008; Accepted April 15, 2008
ABSTRACT
Human Tudor-SN is involved in the degradation of hyper-edited inosine-containing microRNA precursors,thus linking the pathways of RNA interference and editing. Tudor-SN contains four tandem repeats of staphylococcal nuclease-like domains (SN1–SN4) followed by a tudor and C-terminal SN domain (SN5). Here, we showed that Tudor-SN requires tandem repeats of SN domains for its RNA binding and cleavage activity. The crystal structure of a 64-kD truncated form of human Tudor-SN further shows that the four domains, SN3, SN4, tudor and SN5, assemble into a crescent-shaped structure. A concave basic surface formed jointly by SN3 and SN4 domains is likely involved in RNA binding, where citrate ions are bound at the putative RNase active sites. Additional modeling studies provide a structural basis for Tudor-SN’s preference in cleaving RNA containing multiple IU wobble-paired sequences. Collectively, these results suggest that tandem repeats of SN domains in Tudor-SN function as a clamp to capture RNA substrates.
NAR_2008
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