{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:55:55Z","timestamp":1772780155975,"version":"3.50.1"},"reference-count":45,"publisher":"American Society for Cell Biology (ASCB)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p>U2AF is a heterodimeric splicing factor composed of a large (U2AF<jats:sup>65<\/jats:sup>) and a small (U2AF<jats:sup>35<\/jats:sup>) subunit. In humans, alternative splicing generates two U2AF<jats:sup>35<\/jats:sup>variants, U2AF<jats:sup>35<\/jats:sup>a and U2AF<jats:sup>35<\/jats:sup>b. Here, we used RNA interference to specifically ablate the expression of each isoform in HeLa cells. Our results show that knockdown of the major U2AF<jats:sup>35<\/jats:sup>a isoform reduced cell viability and impaired mitotic progression, leading to accumulation of cells in prometaphase. Microarray analysis revealed that knockdown of U2AF<jats:sup>35<\/jats:sup>a affected the expression level of \u223c500 mRNAs, from which &gt;90% were underrepresented relative to the control. Among mRNAs underrepresented in U2AF<jats:sup>35<\/jats:sup>a-depleted cells we identified an essential cell cycle gene, Cdc27, for which there was an increase in the ratio between unspliced and spliced RNA and a significant reduction in protein level. Furthermore, we show that depletion of either U2AF<jats:sup>35<\/jats:sup>a or U2AF<jats:sup>35<\/jats:sup>b altered the ratios of alternatively spliced isoforms of Cdc25B and Cdc25C transcripts. Taken together our results demonstrate that U2AF<jats:sup>35<\/jats:sup>a is essential for HeLa cell division and suggest a novel role for both U2AF<jats:sup>35<\/jats:sup>protein isoforms as regulators of alternative splicing of a specific subset of genes.<\/jats:p>","DOI":"10.1091\/mbc.e06-01-0036","type":"journal-article","created":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:45:15Z","timestamp":1153356315000},"page":"4187-4199","source":"Crossref","is-referenced-by-count":60,"title":["RNA Interference Knockdown of hU2AF<sup>35<\/sup>Impairs Cell Cycle Progression and Modulates Alternative Splicing of Cdc25 Transcripts"],"prefix":"10.1091","volume":"17","author":[{"given":"Teresa Raquel","family":"Pacheco","sequence":"first","affiliation":[{"name":"*Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"}]},{"given":"Lu\u00eds Ferreira","family":"Moita","sequence":"additional","affiliation":[{"name":"*Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"},{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129; and"}]},{"given":"Anita Quintal","family":"Gomes","sequence":"additional","affiliation":[{"name":"*Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"},{"name":"Departamento de Ci\u00eancias da Sa\u00fade, Universidade da Madeira, 9000-390 Funchal, Portugal"}]},{"given":"Nir","family":"Hacohen","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129; and"}]},{"given":"Maria","family":"Carmo-Fonseca","sequence":"additional","affiliation":[{"name":"*Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1038\/sj.onc.1201063","volume":"14","author":"Baldin V.","year":"1997","journal-title":"Oncogene"},{"key":"B2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.cell.2005.02.016","volume":"121","author":"Blower M. 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