title: Tudor staphylococcal nuclease (Tudor-SN) participates in small ribonucleoprotein (snRNP) assembly via interacting with symmetrically dimethylated Sm proteins.
abstract: Human Tudor staphylococcal nuclease (Tudor-SN) is composed of four tandem repeats of staphylococcal nuclease (SN)-like domains, followed by a tudor and SN-like domain (TSN) consisting of a central tudor flanked by two partial SN-like sequences. The crystal structure of the tudor domain displays a conserved aromatic cage, which is predicted to hook methyl groups. Here, we demonstrated that the TSN domain of Tudor-SN binds to symmetrically dimethylarginine (sDMA)-modified SmB/B' and SmD1/D3 core proteins of the spliceosome. We demonstrated that this interaction ability is reduced by the methyltransferase inhibitor 5-deoxy-5-(methylthio)adenosine. Mutagenesis experiments indicated that the conserved amino acids (Phe-715, Tyr-721, Tyr-738, and Tyr-741) in the methyl-binding cage of the TSN domain are required for Tudor-SN-SmB interaction. Furthermore, depletion of Tudor-SN affects the association of Sm protein with snRNAs and, as a result, inhibits the assembly of uridine-rich small ribonucleoprotein mediated by the Sm core complex in vivo. Our results reveal the molecular basis for the involvement of Tudor-SN in regulating small nuclear ribonucleoprotein biogenesis, which provides novel insight related to the biological activity of Tudor-SN.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 30070, China.
authors.forename: Xingjie
authors.initials: X
authors.lastname: Gao
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jinyan
authors.initials: J
authors.lastname: He
authors.forename: Jie
authors.initials: J
authors.lastname: Shao
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Juha
authors.initials: J
authors.lastname: Saarikettu
authors.forename: Olli
authors.initials: O
authors.lastname: Silvennoinen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004720:Endonucleases; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D008745:Methylation; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012261:Ribonucleoproteins / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D008024:Ligands; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D004720:Endonucleases; C095221:SND1 protein, human