{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T13:02:22Z","timestamp":1767272542543,"version":"3.48.0"},"posted":{"date-parts":[[2025,12,3]]},"group-title":"Cell Biology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"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":[[2025,12,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Increasing evidence suggests critical roles of the polycomb-independent transactivation function of EZH2 in promoting some cancers, such as prostate cancer (PCa), yet the underlying mechanism remains poorly understood. Here, we identify the RNA-binding protein NF90 as a key mediator of this activity. NF90 interacts with EZH2, but not with other core components of the polycomb repressive complex 2 (PRC2), through its RNA-binding modules. Conversely, EZH2 engages NF90 via its intrinsically disordered RNA-binding domain in an RNA-dependent manner. NF90 and EZH2 mutually recruit each other to the AR promoter, where they cooperatively activate AR transcription and enhance downstream AR signaling. This NF90-EZH2 complex is essential for PCa cell growth: depletion of either factor abolishes proliferation, an effect rescued by AR re-expression. Similar to EZH2, NF90 promotes cell-cycle gene expression, is upregulated in advanced PCa, and is associated with poor clinical outcomes. Collectively, our findings uncover RNA-mediated protein interactions as a central mechanism underlying PRC2-independent transcriptional activation by EZH2 and establish NF90 as a major EZH2 coactivator, a master regulator of the cell cycle, and a promising therapeutic target in advanced PCa.<\/jats:p>","DOI":"10.64898\/2025.12.02.691892","type":"posted-content","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:49:43Z","timestamp":1765198183000},"source":"Crossref","is-referenced-by-count":0,"title":["RNA-Binding Protein NF90 Mediates Polycomb-Independent Transactivation by EZH2 to Promote Cancer Growth"],"prefix":"10.64898","author":[{"given":"Yuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, Atlanta, GA, USA"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongshun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, Atlanta, GA, USA"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, Emory University School of Medicine, Atlanta, GA, 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan D.","family":"Licht","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Institute, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ximing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan C.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"},{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA"},{"name":"Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, 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