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Biayna, J.* ; Baranovskii, A. ; Chaudhuri, A.* ; Paladin, M.* ; Erdem, B.* ; Keller, L.* ; Barutcu, A.R.* ; Dimmeler, S.* ; Marsico, A. ; Dumbović, G.*

The periphery of nuclear speckles defines a spatially and temporally regulated compartment of long-lived intron-retained RNAs that resolves during mitosis.

Nat. Cell Biol. 28, 1857-1874 (2026)
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Open Access Hybrid
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RNA localization adds a fundamental layer to gene expression by determining when and where translation-ready mRNAs become available, yet how this timing is coordinated with nuclear architecture and cell-cycle progression remains unclear. Here we identify a subnuclear RNA niche at the nuclear speckle periphery that couples 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 that persist for hours and are enriched in transcripts encoding regulators of genome maintenance and mitosis, including centromere and kinetochore assembly, DNA repair and telomere maintenance. Long-lived retained introns exhibit elevated GC content, predicted structural stability and enrichment for nuclear speckle-associated RNA-binding proteins. In interphase, these RNAs localize to a distinct nuclear speckle-peripheral RNA niche in a spatial arrangement conserved across cell types. During mitotic remodelling, they undergo coordinated, kinase-dependent splicing and are released into the cytoplasm of early G1 daughter cells. Together, these findings link cis-encoded intronic features, subnuclear organization and mitotic remodelling to temporal control of RNA fate.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Intron ; Rna Splicing ; Rna ; Mitosis ; Small Nuclear Rna ; Spliceosome ; Cell Nucleus ; Rna-binding Protein ; Telomere; Messenger-rna; Fanconi-anemia; Detained Introns; Splicing Factors; Binding-protein; Gene-expression; Hnrnp F; Retention; Localization; Transcripts
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Journal Nature Cell Biology
Quellenangaben Volume: 28, Issue: 9, Pages: 1857-1874 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants Schwiete stiftung, 80301866
Deutsche Forschungsgemeinschaft (German Research Foundation)