Association of snRNA genes with coiled bodies is mediated by nascent snRNAtranscripts

Background: Coiled bodies are nuclear organelles that are highly enriched i n small nuclear ribonucleoproteins (snRNPs) and certain basal transcription factors. Surprisingly, coiled bodies not only contain mature U snRNPs but also associate with specific chromosomal loci, including gene clusters that encode U snRNAs and histone messenger RNAs. The mechanism(s) by which coil ed bodies associate with these genes is completely unknown. Results: Using stable cell lines, we show that artificial tandem arrays of human U1 and U2 snRNA genes colocalize with coiled bodies and that the freq uency of the colocalization depends directly on the transcriptional activit y of the array. Association of the genes with coiled bodies was abolished w hen the artificial U2 arrays contained promoter mutations that prevent tran scription or when RNA polymerase II transcription was globally inhibited by alpha-amanitin. Remarkably, the association was also abolished when the U2 snRNA coding regions were replaced by heterologous sequences. Conclusions: The requirement for the U2 snRNA coding region indicates that association of snRNA genes with coiled bodies is mediated by the nascent U2 RNA itself, not by DNA or DNA-bound proteins. Our data provide the first e vidence that association of genes with a nuclear organelle can be directed by an RNA and suggest an autogenous feedback regulation model.