The coilin interactome identifies hundreds of small noncoding RNAs that traffic through Cajal bodies

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Martin Machyna - , Yale University (Author)
  • Stephanie Kehr - , University Hospital Leipzig (Author)
  • Korinna Straube - , Yale University (Author)
  • Dennis Kappei - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Frank Buchholz - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Falk Butter - , Institute of Molecular Biology (IMB) gGmbH (Author)
  • Jernej Ule - , University College London (Author)
  • Jana Hertel - , University Hospital Leipzig (Author)
  • Peter F Stadler - , University Hospital Leipzig (Author)
  • Karla M Neugebauer - , Yale University (Author)

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.

Details

Original languageEnglish
Pages (from-to)389-399
Number of pages11
JournalMolecular Cell
Volume56
Issue number3
Publication statusPublished - 6 Nov 2014
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84921357711
PubMed 25514182

Keywords

Keywords

  • Animals, Cell Cycle, Cell Nucleolus/metabolism, Coiled Bodies/metabolism, HeLa Cells, Humans, Mice, Nuclear Proteins/metabolism, Protein Binding, RNA Transport, RNA, Small Untranslated/metabolism