title: Structural and functional insights into human Tudor-SN, a key component linking RNA interference and editing.
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 I.U wobble-paired sequences. Collectively, these results suggest that tandem repeats of SN domains in Tudor-SN function as a clamp to capture RNA substrates.
authors.affiliation: Institute of Molecular Biology, Academia Sinica and Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Chia-Lung
authors.initials: CL
authors.lastname: Li
authors.forename: Wei-Zen
authors.initials: WZ
authors.lastname: Yang
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Hanna S
authors.initials: HS
authors.lastname: Yuan
mesh_terms: D018360:Crystallography, X-Ray; D004720:Endonucleases; D006801:Humans; D008836:Micrococcal Nuclease / Q000737:chemistry; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D017393:RNA Editing; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012313:RNA; D004720:Endonucleases; C095221:SND1 protein, human; D008836:Micrococcal Nuclease