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Here, we investigated the RNA polymerase II (Pol II) dynamics during rapid cytokine-induced activation in NK cells. Brief exposure to the proinflammatory cytokine interleukin-12 (IL-12) elicited rapid, genome-wide redistribution of Pol II within minutes, with increased promoter-proximal Pol II pausing at effector loci including Ifng. This IL-12\u2013induced Pol II reorganization was mediated by the transcription factor STAT4. We further identified the RNA helicase DDX5 as a STAT4 interaction partner required for optimal IFN-\u03b3 production and appropriate modulation of Pol II occupancy following IL-12 stimulation. Together, these findings identify STAT4\/DDX5-mediated regulation of Pol II as a critical mechanism enabling the rapid responsiveness of NK cells to proinflammatory cytokines.<\/jats:p>","DOI":"10.1084\/jem.20250995","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:21:02Z","timestamp":1780035662000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-12 induces rapid STAT4\/DDX5-dependent remodeling of RNA polymerase II occupancy in NK cells"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6452-8152","authenticated-orcid":true,"given":"Hyunu","family":"Kim","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center 1 , New York, NY,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Louis V. 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