222: snaR-A disrupts mRNA splicing in cancer

Zhou S et al., Nat Commun - This episode examines how the cancer-associated Pol III transcript snaR-A binds core splicing factors, localizes near nuclear speckles, perturbs U2-dependent splicing to increase intron retention, and promotes cell proliferation linked to poorer patient outcomes. Key terms: snaR-A, splicing, SF3B2, intron retention, nuclear speckles. Study Highlights:Proteomic pull-downs and CLIP analyses reveal snaR-A interactions with RNA chaperones (La, ILF3) and multiple splicing factors, with PAR-CLIP and CLIP-qPCR supporting a direct interaction with the U2 snRNP subunit SF3B2. HCR-RNA-FISH and SON TSA-seq place snaR-A in subnuclear foci adjacent to nuclear speckles and show snaR-A gene clusters are speckle-proximal. Functional genomics show snaR-A overexpression increases intron retention while snaR-A depletion reduces intron retention and enhances splicing of transcripts marked by high U2 occupancy and speckle proximity, and snaR-A overexpression selectively reduces SF3B2 protein levels. Phenotypically, snaR-A depletion lowers proliferation in HEK293T cells, snaR-A gene activity correlates with proliferation markers across primary tumors and predicts worse survival, and rescued splicing increases protein abundance for tumor-suppressive targets such as OGFR. Conclusion:snaR-A acts as a nuclear antagonist of U2-dependent splicing near speckles, promoting cell proliferation and providing a non-mutational route to splicing dysregulation in cancer Music:Enjoy the music based on this article at the end of the episode. First author:Zhou S Journal:Nature Communications DOI:10.1038/s41467-025-65448-x Reference:Zhou S, Lizarazo S, Chorghade S, Mouli L, Cheng R, KC R, Kalsotra A, Van Bortle K. Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations. Nat Commun. 2025;16:10460. https://doi.org/10.1038/s41467-025-65448-x License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/snar-a-splicing-disruption ️ Episode:222: snaR-A hijacks splicing to drive proliferation ️ Season:1 Article title:Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-08. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the transcript's core mechanistic and phenotypic claims described in the Nature Communications article: snaR-A interactions with SF3B2 and splicing machinery, subnuclear speckle localization, intron retention changes with overexpression/depletion, effects on proliferation and OGFR, and clinical correlations.- transcript topics: Pol III overactivity and snaR-A origin in cancer; snaR-A interactions with splicing factors (SF3B2, U2 snRNP); subnuclear localization near nuclear speckles; intron retention and splicing efficiency changes; effects of snaR-A depletion/overexpression on proliferation and OGFR; clinical associations: snaR-A activity and patient survival QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- met...