Alu repeat-containing RNA organizes actively transcribed genomic regions around nuclear speckle for co-transcriptional RNA processing

ABSTRACT: It has long been known that nuclear speckle is a nuclear body that contains numerous RNA splicing and processing proteins. Accumulating evidences have shown that the genomic regions of highly transcribed genes and their corresponding nascent pre­mRNAs are organized around nuclear speckles to achieve co-transcriptional RNA processing. But, how the actively transcribed genes are organized around nuclear speckle is unknown. Here, we identified RNAs localized in nuclear speckles and found that a class of Alu-repeat RNAs were highly enriched around the nuclear speckle. These RNAs tend to directly bind to the genomic regions of actively transcribed genes via its Alu element and form R-loops. Meanwhile, they can interact with nuclear speckle protein components and promote their aggregation and phase separation, synchronously mediating the formation of nuclear speckle and organization of the actively transcribed genes around them. Depletion of these Alu-repeat RNAs results in a significant reduction in the size of nuclear speckle, far away of active genes from nuclear speckle, and the consequent reduction in RNA processing. This mechanism is essential for the high expression of a large number of erythroid specific genes during erythrocyte development, which would be severely impeded in the absence of these repeat-containing RNAs. Our work highlights the emerging role of Alu-repeat RNAs in assembling nuclear speckles and mediating spatial co-transcriptional RNA processing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281381 | GEO | 2026/03/03

REPOSITORIES: GEO