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Here, we applied a combination of genomic and biochemical approaches to study the biogenesis and subsequent protein interactions of snaR-A and to better understand its role as a putative driver of cancer progression. By profiling the chromatin landscapes across a multitude of primary tumor types, we show that predicted snaR-A upregulation is broadly linked with unfavorable outcomes among cancer patients. At the molecular level, we unexpectedly discover widespread interactions between snaR-A and mRNA splicing factors, including SF3B2 - a core component of the U2 small nuclear ribonucleoprotein (snRNP). We find that SF3B2 levels are sensitive to high snaR-A abundance and that depletion of snaR-A alone is sufficient to decrease intron retention levels across subpopulations of mRNA enriched for U2 snRNP occupancy. snaR-A sensitive genes are characterized by high GC content, close spatial proximity to nuclear bodies concentrated in pre-mRNA splicing factors, and functional enrichment for proteins involved in deacetylation and autophagy. We highlight examples of splicing misregulation and increased protein levels following snaR-A depletion for a wide-ranging set of factors, suggesting snaR-A-driven splicing defects may have far-reaching effects that re-shape the cellular proteome. These findings clarify the molecular activities and consequences of snaR-A in cancer, and altogether establish a novel mechanism through which Pol III overactivity may promote tumorigenesis.<\/jats:p>","DOI":"10.1101\/2024.07.02.601767","type":"posted-content","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:20:12Z","timestamp":1720052412000},"source":"Crossref","is-referenced-by-count":2,"title":["Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7132-1560","authenticated-orcid":false,"given":"Sihang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lizarazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leela","family":"Mouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip","family":"Chorghade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiying","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K C","family":"Rajendra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auinash","family":"Kalsotra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0733-0830","authenticated-orcid":false,"given":"Kevin","family":"Van Bortle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024070510551208000_2024.07.02.601767v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1782"},{"key":"2024070510551208000_2024.07.02.601767v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1145"},{"key":"2024070510551208000_2024.07.02.601767v1.3","doi-asserted-by":"publisher","DOI":"10.1101\/gad.333989.119"},{"key":"2024070510551208000_2024.07.02.601767v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1984.tb02294.x"},{"key":"2024070510551208000_2024.07.02.601767v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/hdy.2011.43"},{"key":"2024070510551208000_2024.07.02.601767v1.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-06-02382.1993"},{"key":"2024070510551208000_2024.07.02.601767v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm668"},{"key":"2024070510551208000_2024.07.02.601767v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm244"},{"key":"2024070510551208000_2024.07.02.601767v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq856"},{"key":"2024070510551208000_2024.07.02.601767v1.10","doi-asserted-by":"publisher","DOI":"10.22088\/IJMCM.BUMS.10.4.258"},{"key":"2024070510551208000_2024.07.02.601767v1.11","doi-asserted-by":"publisher","DOI":"10.1177\/1010428317707374"},{"key":"2024070510551208000_2024.07.02.601767v1.12","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.11224"},{"key":"2024070510551208000_2024.07.02.601767v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28136"},{"key":"2024070510551208000_2024.07.02.601767v1.14","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2019.10258"},{"key":"2024070510551208000_2024.07.02.601767v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111264"},{"key":"2024070510551208000_2024.07.02.601767v1.16","doi-asserted-by":"publisher","DOI":"10.1261\/rna.078694.121"},{"key":"2024070510551208000_2024.07.02.601767v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.07.152"},{"key":"2024070510551208000_2024.07.02.601767v1.18","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2009.74.038"},{"key":"2024070510551208000_2024.07.02.601767v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2764"},{"key":"2024070510551208000_2024.07.02.601767v1.20","doi-asserted-by":"crossref","unstructured":"Therneau, T.M. , and Grambsch, P.M. 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