{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T08:05:11Z","timestamp":1775894711784,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,14]]},"group-title":"Molecular Biology","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,14]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Intron removal from pre-mRNA is catalyzed by the spliceosome, which comprises 5 snRNPs containing small nuclear RNAs (snRNAs). U2 snRNA makes critical RNA-RNA and RNA-protein contacts throughout the splicing cycle. Mutations in U2 snRNA, particularly at position C28, have been linked to cancers. To study gene expression changes mediated by mutated U2 snRNAs, U2-2 C28 mutants, U2-2 knockout (KO), and U2-2 overexpression (OE) cell lines were constructed followed by RNA sequencing. We observed significant changes in splicing and over 4,000 differentially expressed genes enriched in pathways like RNA processing and non-coding RNAs upon knocking out U2-2 snRNA. Splicing patterns were more influenced by U2-2 dosage than mutations alone. Therefore, the mutant exhibits a compound phenotype, resulting from reduced U2-2 levels (and thus mostly phenocopying the KO) and additional mutant-specific splicing changes.<\/jats:p>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>U2-2 snRNA BSL mutants alter splicing and the transcriptome<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>U2-2 KO phenocopies most altered splice events in the mutants<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Both U2-2 levels and mutations alter splicing<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Many altered splice events lead to NMD<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.12.642709","type":"posted-content","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T23:00:31Z","timestamp":1741993231000},"source":"Crossref","is-referenced-by-count":1,"title":["U2-2 snRNA Mutations Alter the Transcriptome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3680-5452","authenticated-orcid":false,"given":"Zhongxuan","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-0486","authenticated-orcid":false,"given":"Varun","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7692-2496","authenticated-orcid":false,"given":"Charles","family":"Query","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041100371945000_2025.03.12.642709v1.1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017007062"},{"key":"2026041100371945000_2025.03.12.642709v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310249110"},{"key":"2026041100371945000_2025.03.12.642709v1.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0242126"},{"key":"2026041100371945000_2025.03.12.642709v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2024.03.012"},{"key":"2026041100371945000_2025.03.12.642709v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature11547"},{"key":"2026041100371945000_2025.03.12.642709v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-022-00292-2"},{"key":"2026041100371945000_2025.03.12.642709v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.02.016"},{"key":"2026041100371945000_2025.03.12.642709v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/CBIC.202300864"},{"key":"2026041100371945000_2025.03.12.642709v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2777"},{"key":"2026041100371945000_2025.03.12.642709v1.10","doi-asserted-by":"crossref","unstructured":"Cheng, Y. , Lund, E. , Kahan, B. 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