The periphery of nuclear speckles defines a spatially and temporally regulated compartment of long-lived intron-retained RNAs that resolves during mitosis
Ontology highlight
ABSTRACT: RNA localization adds a fundamental layer to gene expression by determining when and where translation-ready mRNAs become available. Here, we identify a distinct subnuclear RNA niche at the nuclear speckle periphery that links intron retention to cell-cycle-timed RNA release. Using compartment-resolved transcriptional inhibition, sequence-based deep learning, and single-molecule and super-resolution RNA imaging in human pluripotent stem cells, we define a class of nuclear RNAs with long-lived retained introns (LL-IR-RNAs) that maintain stable intron retention for hours and are enriched in genome maintenance and mitosis regulators, including centromere and kinetochore assembly, DNA repair, and telomere maintenance. Long-lived retained introns are characterized by elevated GC content, predicted structural stability, and nuclear speckle-associated RBPs. In interphase, LL-IR-RNAs localize to a nuclear speckle-proximal niche conserved between cell types. During mitotic remodeling, they undergo coordinated, kinase-dependent splicing and populate the cytoplasm of early G1 daughter cells. These findings link cis-encoded intronic features, subnuclear organization and mitotic remodeling to temporal control of RNA fate.
ORGANISM(S): Homo sapiens
PROVIDER: GSE327794 | GEO | 2026/06/24
REPOSITORIES: GEO
ACCESS DATA