Nuclear speckles are gene expression nodes where transcription and RNA processing take place. Yet, the mechanisms underlying the spatial organization of nuclear speckles are unclear. In this study, Liu et al. report that Alu repeat-containing RNAs are enriched in nuclear speckles and tend to bind actively transcribed genes.

Using BGLT3 as an example, the authors showed that BGLT3 Alu-containing region interacts with DNA targets via R-loop formation and direct their target genes to nuclear speckles in an Alu-dependent manner. Integration of ChIRP–seq (chromatin isolation by RNA purification with sequencing) and RNA-sequencing data following depletion of Alu-containing RNA revealed downregulation of genes involved in erythroid differentiation. Live imaging following overexpression or knock down of BGLT3 indicated that Alu repeat-containing RNAs influence the size and mobility of nuclear speckles.