Systematic mapping of nuclear domain-associated transcripts reveals speckles and lamina as hubs of functionally distinct retained introns
Raw files for microscopy and western blot data presented in this study. *AR. Barutcu and M. Wu equally contributed to this study. SUMMARY The nucleus is highly compartmentalized through the formation of distinct classes of membraneless domains, yet the composition and function of many of these structures is not well understood. Using APEX2-mediated proximity labelling and RNA sequencing, we surveyed transcripts associated with nuclear speckles, several additional domains, and the lamina. Remarkably, speckles and lamina are associated with distinct classes of retained introns enriched in genes that function in RNA processing, translation, and the cell cycle. In contrast to the lamina-proximal introns, retained introns associated with speckles are relatively short, GC-rich, and enriched for functional sites of RNA binding proteins that are concentrated in these domains. They are also highly differentially regulated across diverse cellular contexts, including the cell cycle. Our study thus provides a resource of nuclear domain-associated transcripts and further reveals speckles and lamina as hubs of distinct populations of retained introns linked to gene regulation and cell cycle progression.