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Frey Award for Breakthrough Scientists"]}],"id":[{"id":"https:\/\/ror.org\/01gd7b947","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["DGE-2139841"],"award-info":[{"award-number":["DGE-2139841"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,29]]},"abstract":"<jats:p>Herpesviruses, including the oncogenic human pathogen Kaposi\u2019s Sarcoma-associated herpesvirus (KSHV), rely on cellular RNA Polymerase II (RNAPII) for expression of their protein-coding genes. Late in the lytic cycle, transcription initiation on a subset of KSHV genes depends on ORF24, a viral transcriptional activator that binds to viral late promoters through structural mimicry of a host transcription factor. Here, we present a structure of the N-terminal domain of ORF24, and show that it adopts a novel fold that facilitates direct binding of the RNAPII C-terminal domain (CTD). We further show that ORF24 is highly sensitive to the phosphorylation state of the RNAPII CTD, allowing for selective binding of the hypophosphorylated form to viral preinitiation complexes. By combining promoter binding and polymerase recruitment into a single protein, KSHV has streamlined essential steps in transcription complex assembly. Our work lays the groundwork for mechanistic dissection of a viral preinitiation complex.<\/jats:p>","DOI":"10.64898\/2026.06.29.734287","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:25:18Z","timestamp":1782793518000},"source":"Crossref","is-referenced-by-count":0,"title":["Kaposi\u2019s Sarcoma-associated herpesvirus uses a novel protein fold to hijack RNA Polymerase II for viral late gene transcription"],"prefix":"10.64898","author":[{"given":"Pankaj Kumar","family":"Madheshiya","sequence":"first","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Doak","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Gierke","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3904-492X","authenticated-orcid":false,"given":"Shaogeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Wu Tsai Institute, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7277-5233","authenticated-orcid":false,"given":"Allison L.","family":"Didychuk","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070201350878000_2026.06.29.734287v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4582"},{"key":"2026070201350878000_2026.06.29.734287v1.2","doi-asserted-by":"crossref","unstructured":"Llacsahuanga-Allcca, L.E. , Didychuk, A.L. , Rodriguez-Vargas, A. & Glaunsinger, B.A. The Kaposi\u2019s sarcoma-associated herpesvirus TBP mimic uses a noncanonical DNA-binding mode to promote viral late gene transcription. 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