{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:51:51Z","timestamp":1793263911526,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM127473"],"award-info":[{"award-number":["R01GM127473"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM136426"],"award-info":[{"award-number":["R35GM136426"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM118136"],"award-info":[{"award-number":["R35GM118136"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"HHS | NIH | National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R21HG012624"],"award-info":[{"award-number":["R21HG012624"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007186","name":"UC | UCLA | Jonsson Comprehensive Cancer Center, University of California, Los Angeles","doi-asserted-by":"publisher","award":["SEED2021"],"award-info":[{"award-number":["SEED2021"]}],"id":[{"id":"10.13039\/100007186","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007186","name":"UC | UCLA | Jonsson Comprehensive Cancer Center, University of California, Los Angeles","doi-asserted-by":"publisher","award":["VISION2024"],"award-info":[{"award-number":["VISION2024"]}],"id":[{"id":"10.13039\/100007186","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>\n                    Myelodysplastic syndromes and other cancers are often associated with mutations in the U2 snRNP protein SF3B1. Common SF3B1 mutations, including K700E, disrupt SF3B1 interaction with the protein SUGP1 and induce aberrant activation of alternative 3\u2032 splice sites (ss), presumably resulting from aberrant U2\/branch site (BS) recognition by the mutant spliceosome. Here, we apply a method of U2 IP-seq to profile BS binding across the transcriptome of K562 leukemia cells carrying the\n                    <jats:italic>SF3B1<\/jats:italic>\n                    K700E mutation. For alternative 3\u2032 ss activated by K700E, we identify their associated BSs and show that they are indeed shifted from the WT sites. Unexpectedly, we also identify thousands of additional changes in BS binding in the mutant cells that do not alter splicing. These new BSs are usually very close to the natural sites, occur upstream or downstream, and either exhibit stronger base-pairing potential with U2 snRNA or are adjacent to stronger polypyrimidine tracts than the WT sites. The widespread imprecision in BS recognition induced by K700E with limited changes in 3\u2032 ss selection expands the physiological consequences of this oncogenic mutation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2423776122","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T13:42:05Z","timestamp":1742996525000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["Cancer-associated SF3B1 mutation K700E causes widespread changes in U2\/branchpoint recognition without altering splicing"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9845-913X","authenticated-orcid":false,"given":"Andrey","family":"Damianov","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, David Geffen School of Medicine, University of California,","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-9648","authenticated-orcid":false,"given":"Chia-Ho","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, David Geffen School of Medicine, University of California,","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-1471","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Manley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2705-8187","authenticated-orcid":false,"given":"Douglas L.","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, David Geffen School of Medicine, University of California,","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10496"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00541-7"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.07.019"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.07.003"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-633537"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1032"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10615"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1038\/s41375-022-01728-5","article-title":"SF3B1 mutated MDS: Blast count, genetic co-abnormalities and their impact on classification and prognosis","volume":"36","author":"Huber S.","year":"2022","unstructured":"S. Huber , SF3B1 mutated MDS: Blast count, genetic co-abnormalities and their impact on classification and prognosis. Leukemia 36, 2894\u20132902 (2022).","journal-title":"Leukemia"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.053"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.07.017"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004105"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202301955"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-091719-064225"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2019.1691497"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03789-5"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07458-1"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.8.4752"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922622117"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01507-5"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2216712119"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.06.003"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.078977.121"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.113223","article-title":"Splicing quality control mediated by DHX15 and its G-patch activator SUGP1","volume":"42","author":"Feng Q.","year":"2023","unstructured":"Q. Feng, K. Krick, J. Chu, C. B. Burge, Splicing quality control mediated by DHX15 and its G-patch activator SUGP1. Cell Rep. 42 (2023).","journal-title":"Cell Rep."},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.351154.123"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.04.006"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.291872.116"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/jb\/mvac049","article-title":"Cancer-associated mutations in SF3B1 disrupt the interaction between SF3B1 and DDX42","volume":"172","author":"Zhao B.","year":"2022","unstructured":"B. Zhao , Cancer-associated mutations in SF3B1 disrupt the interaction between SF3B1 and DDX42. J. Biochem. 172, 117\u2013126 (2022).","journal-title":"J. Biochem."},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s41467-023-36489-x","article-title":"Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly","volume":"14","author":"Yang F.","year":"2023","unstructured":"F. Yang , Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly. Nat. Commun. 14, 897 (2023).","journal-title":"Nat. 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Ruskin, J. M. Greene, M. R. Green, Cryptic branch point activation allows accurate in vitro splicing of human \u03b2-globin intron mutants. Cell 41, 833\u2013844 (1985).","journal-title":"Cell"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac287"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1042"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.248625.114"},{"key":"e_1_3_4_50_2","unstructured":"A. Damianov U2 IP-seq from K562 cells expressing SF3B1-3xFlag WT or SF3B1-3xFlag K700E. NCBI GEO. https:\/\/doi.org\/10.22033\/ESGF\/CMIP6.7673. Deposited 30 October 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2423776122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T13:45:20Z","timestamp":1742996720000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2423776122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":50,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1073\/pnas.2423776122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2423776122","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.11.18.624191","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,26]]},"assertion":[{"value":"2024-11-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2423776122"}}