296: snaR-A ncRNA antagonizes U2 snRNP SF3B2 to drive intron retention in human cells

Zhou S et al., Nature Communications, doi:10.1038/s41467-025-65448-x - snaR-A noncoding RNA interacts with U2 snRNP subunit SF3B2 and nuclear speckles, increasing intron retention and promoting proliferation in human cancer-relevant cells. Key terms: snaR-A, SF3B2, intron retention, nuclear speckles, RNA polymerase III. Study Highlights:Using human cell lines (HEK293T, A549, THP-1) and tumor chromatin data, the authors combined biotinylated RNA pulldown mass spectrometry, PAR-CLIP/CLIP-qPCR, HCR-RNA-FISH, TSA-seq, and ultra-deep RNA-seq (IRFinder, rMATS) to map snaR-A interactions and splicing outcomes. snaR-A directly binds splicing factors and shows nucleotide-level crosslinking to the U2 snRNP protein SF3B2, and localizes to subnuclear foci adjacent to nuclear speckles and U6-containing sites. Functionally, snaR-A overexpression increases intron retention and selectively depletes SF3B2 protein, whereas snaR-A depletion reduces intron retention for transcripts with high U2 occupancy and speckle proximity. These splicing changes alter protein abundance for multiple targets and coincide with reduced proliferation after snaR-A depletion, consistent with tumor-level associations to growth. Conclusion:snaR-A acts as a molecular antagonist of U2-dependent splicing by interacting with SF3B2 and perturbing processing of specific mRNA subpopulations, promoting intron retention and proliferation in cancer-relevant contexts. Music:Enjoy the music based on this article at the end of the episode. Article title:Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations First author:Zhou S Journal:Nature Communications, doi:10.1038/s41467-025-65448-x DOI:10.1038/s41467-025-65448-x Reference:Zhou S., Lizarazo S., Chorghade S., Mouli L., Cheng R., Rajendra K. C., Kalsotra A., Van Bortle K. Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations. Nature Communications. 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-sf3b2-splicing QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-21. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the transcript’s presentation of the snaR-A study: interaction with SF3B2 and U2 snRNP, localization to nuclear speckles, intron retention effects, SF3B2 protein depletion, depletion effects on splicing and protein abundance, proliferation/migration phenotypes, TCGA prognosis, and limitations.- transcript topics: snaR-A interaction with SF3B2 and U2 snRNP; localization of snaR-A to nuclear speckles and proximity to U6; snaR-A-induced intron retention and splicing disruption; SF3B2 protein depletion upon snaR-A overexpression; snaR-A depletion reduces IR in U2-residency, speckle-proximal transcripts; OGFR and other targets affected by splicing changes QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi Chapters (00:00:20) - Cancer's editing room: The heist(00:03:27) - The SNAR A saboteur(00:07:14) - Snarra disrupts the splicing machinery(00:11:53) - Snare A in lung cancer(00:16:50) - A whisper in the dark