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While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood. Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex. HuR-dependent NK cell expansion contributed to long-term cytomegalovirus control and facilitated control of subcutaneous tumors but not tumor metastases in two independent tumor models. These results show that posttranscriptional regulation by HuR specifically affects NK cell expansion, which is required for the control of long-term virus infection and solid tumors, but not acute infection or tumor metastases, highlighting fundamental differences with antigen-specific T cell control.<\/jats:p>","DOI":"10.1084\/jem.20231154","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T02:21:01Z","timestamp":1691547661000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["NK cell expansion requires HuR and mediates control of solid tumors and long-term virus infection"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-3556","authenticated-orcid":true,"given":"Sytse J.","family":"Piersma","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cf69335","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Division of Rheumatology, Department of Medicine, , St. Louis, MO, USA"},{"name":"Siteman Cancer Center, Washington University School of Medicine 2 , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-0783","authenticated-orcid":true,"given":"Sushant","family":"Bangru","sequence":"additional","affiliation":[{"name":"University of Illinois Urbana-Champaign 3 Department of Biochemistry, , Champaign, IL, USA"},{"name":"Cancer Center at Illinois, University of Illinois Urbana-Champaign 4 , Champaign, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4913-7178","authenticated-orcid":true,"given":"Jeesang","family":"Yoon","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cf69335","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Division of Rheumatology, Department of Medicine, , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6367-852X","authenticated-orcid":true,"given":"Tom W.","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cf69335","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Division of Rheumatology, Department of Medicine, , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-0292","authenticated-orcid":true,"given":"Liping","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cf69335","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Division of Rheumatology, Department of Medicine, , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5976-9250","authenticated-orcid":true,"given":"Chyi-Song","family":"Hsieh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cf69335","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Division of Rheumatology, Department of Medicine, , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6389-561X","authenticated-orcid":true,"given":"Beatrice","family":"Plougastel-Douglas","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04cf69335","id-type":"ROR","asserted-by":"publisher"}],"name":"Washington University School of Medicine 1 Division of Rheumatology, Department of Medicine, , St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1011-0006","authenticated-orcid":true,"given":"Auinash","family":"Kalsotra","sequence":"additional","affiliation":[{"name":"University of Illinois Urbana-Champaign 3 Department of Biochemistry, , Champaign, IL, USA"},{"name":"Cancer Center at Illinois, University of Illinois Urbana-Champaign 4 , Champaign, IL, USA"},{"name":"Carl R. 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