biostudies-literatureMcIntyre ABREC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)Swiss National Science FoundationEuropean Molecular Biology Organization (EMBO)390https://www.ebi.ac.uk/biostudies/studies/S-EPMC11700124biostudies-literatureUnknown16(1)Nuclear speckles are membraneless organelles that associate with active transcription sites and participate in post-transcriptional mRNA processing. During the cell cycle, nuclear speckles dissolve following phosphorylation of their protein components. Here, we identify the PP1 family as the phosphatases that counteract kinase-mediated dissolution. PP1 overexpression increases speckle cohesion and leads to retention of mRNA within speckles and the nucleus. Using APEX2 proximity labeling combined with RNA-sequencing, we characterize the recruitment of specific RNAs. We find that many transcripts are preferentially enriched within nuclear speckles compared to the nucleoplasm, particularly chromatin- and nucleus-associated transcripts. While total polyadenylated RNA retention increases with nNature communicationsPhosphorylation of a nuclear condensate regulates cohesion and mRNA retention.PMC11700124192622ALTF 978-2019101029269310030Walser SRai AKTschan ABMeyer KFujita KMcIntyre ABRPelkmans LfalsePhosphorylation of a nuclear condensate regulates cohesion and mRNA retention.Nuclear speckles are membraneless organelles that associate with active transcription sites and participate in post-transcriptional mRNA processing. During the cell cycle, nuclear speckles dissolve following phosphorylation of their protein components. Here, we identify the PP1 family as the phosphatases that counteract kinase-mediated dissolution. PP1 overexpression increases speckle cohesion and leads to retention of mRNA within speckles and the nucleus. Using APEX2 proximity labeling combined with RNA-sequencing, we characterize the recruitment of specific RNAs. We find that many transcripts are preferentially enriched within nuclear speckles compared to the nucleoplasm, particularly chromatin- and nucleus-associated transcripts. While total polyadenylated RNA retention increases with n2025-01-01T00:00:00Z2025 Jan2026-04-08T19:53:20.037Z2026-04-08T14:31:26.829ZS-EPMC117001243975567510.1038/s41467-024-55469-3