title: A role for SUMOylation in snoRNP biogenesis revealed by quantitative proteomics.
abstract: A role for SUMOylation in the biogenesis and/or function of Box C/D snoRNPs has been reported, mediated via SUMO2 conjugation to the core snoRNP protein, Nop58. A quantitative proteomics screen, based on SILAC (stable-isotope labeling by amino acids in cell culture) and mass spectrometry using extracts prepared from cultured mammalian cells expressing either 6His-SUMO1 or -SUMO2, revealed that the snoRNP-related proteins Nop58, Nhp2, DKC1 and NOLC1 are amongst the main SUMO-modified proteins in the nucleolus. SUMOylation of Nhp2 and endogenous Nop58 was confirmed using a combination of in vitro and cell-based assays and the modified lysines identified by site-directed mutagenesis. SUMOylation of Nop58 was found to be important for high-affinity Box C/D snoRNA binding and the localization of newly transcribed snoRNAs to the nucleolus. Here, these findings are reviewed and a model for understanding Nop58 SUMOylation in the context of Box C/D snoRNP biogenesis is presented. Given the essential role of snoRNPs in the modification of pre-ribosomal RNA, this work suggests that SUMO, snoRNPs and ribosome assembly, and thus cellular translation, growth and proliferation, may be linked via novel mechanisms which warrant further investigation.
authors.affiliation: Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, UK.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Westman
authors.forename: Angus I
authors.initials: AI
authors.lastname: Lamond
mesh_terms: D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D040901:Proteomics; D020537:RNA, Small Nucleolar / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
chemical_list: C416929:NHP2 protein, human; C499062:NOP58 protein, human; D009687:Nuclear Proteins; D020537:RNA, Small Nucleolar; D017411:Ribonucleoproteins, Small Nuclear; D020718:Ribonucleoproteins, Small Nucleolar; D025841:Small Ubiquitin-Related Modifier Proteins