title: The coilin interactome identifies hundreds of small noncoding RNAs that traffic through Cajal bodies.
abstract: Coilin protein scaffolds Cajal bodies (CBs)-subnuclear compartments enriched in small nuclear RNAs (snRNAs)-and promotes efficient spliceosomal snRNP assembly. The molecular function of coilin, which is intrinsically disordered with no defined motifs, is poorly understood. We use UV crosslinking and immunoprecipitation (iCLIP) to determine whether mammalian coilin binds RNA in vivo and to identify targets. Robust detection of snRNA transcripts correlated with coilin ChIP-seq peaks on snRNA genes, indicating that coilin binding to nascent snRNAs is a site-specific CB nucleator. Surprisingly, several hundred small nucleolar RNAs (snoRNAs) were identified as coilin interactors, including numerous unannotated mouse and human snoRNAs. We show that all classes of snoRNAs concentrate in CBs. Moreover, snoRNAs lacking specific CB retention signals traffic through CBs en route to nucleoli, consistent with the role of CBs in small RNP assembly. Thus, coilin couples snRNA and snoRNA biogenesis, making CBs the cellular hub of small ncRNA metabolism.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany; Department of Molecular Biophysics & Biochemistry, Yale University, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Machyna
authors.affiliation: Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kehr
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany; Department of Molecular Biophysics & Biochemistry, Yale University, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Korinna
authors.initials: K
authors.lastname: Straube
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kappei
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Buchholz
authors.affiliation: Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Butter
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Jernej
authors.initials: J
authors.lastname: Ule
authors.affiliation: Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Hertel
authors.affiliation: Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany; Department of Molecular Biophysics & Biochemistry, Yale University, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: karla.neugebauer@yale.edu.
authors.forename: Karla M
authors.initials: KM
authors.lastname: Neugebauer
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002466:Cell Nucleolus / Q000378:metabolism; D020541:Coiled Bodies / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D034443:RNA Transport; D058727:RNA, Small Untranslated / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D058727:RNA, Small Untranslated; C068921:p80-coilin