Alu repeat-containing RNA spatially organizes actively transcribed genomic regions around nuclear speckle

ABSTRACT: Nuclear speckles are nuclear bodies enriched with RNA processing proteins. Highly transcribed genes and their nascent pre­mRNAs are organized around nuclear speckles, facilitating co-transcriptional RNA processing. However, the mechanism underlying this spatial organization remains unclear. Here, we identified a class of Alu repeat-containing RNAs that are highly enriched in nuclear speckles. These RNAs interact with actively transcribed genes through their Alu elements, partially via R-loop formation. They also engage with nuclear speckle proteins promoting their aggregation, phase separation and assembly of nuclear speckles, thereby orchestrating the spatial organization of actively transcribed genes around these structures. Depleting these RNAs reduces speckle size, displaces active genes and impairs RNA processing. Moreover, this mechanism is critical for high expression of many erythroid differentiation genes during erythropoiesis. Our findings highlight the pivotal role of Alu repeat-containing RNAs in nuclear speckles assembly and their function in mediating spatial co-transcriptional RNA processing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE313867 | GEO | 2026/03/03

REPOSITORIES: GEO