The Coilin Interactome Identifies Hundreds of Small Noncoding RNAs that Traffic through Cajal Bodies

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. [Display omitted] •The Cajal body (CB) scaffolding protein, coilin, binds directly to snRNAs and snoRNAs•Coilin accumulates on active sites of snRNA and histone gene transcription•Intron-encoded snoRNAs traffic through CBs before accumulating in nucleoli•Cajal bodies are the cellular hub of small noncoding RNA metabolism Using ChIP-seq and iCLIP, Machyna et al. show that Cajal bodies (CBs) accumulate at sites of active snRNA and histone gene transcription. Additionally, intron-encoded snoRNAs detour through CBs en route to nucleoli, suggesting that CBs are hubs for small noncoding RNAs.