{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:55:53Z","timestamp":1790362553527,"version":"4.1.0"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"28","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271314"],"award-info":[{"award-number":["32271314"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32090014"],"award-info":[{"award-number":["32090014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:p>Nairoviruses are emerging tick-borne pathogens for which effective antiviral therapies are currently unavailable. Although nucleoproteins (NPs) are essential for viral genome encapsulation and have been extensively characterized at the structural level, whether they perform additional functions during viral replication remains unclear. Here, we investigated the NP of the representative nairovirus Tacheng tick virus 1 (TcTV1). We found that the TcTV1 NP binds to nucleic acids in a sequence-independent manner and assembles into tetramer-based ribonucleoprotein complexes upon nucleic acid binding. This assembly process is accompanied by a pronounced conformational rearrangement that facilitates NP polymerization. In addition to its role in RNA encapsulation, TcTV1 NP exhibits intrinsic endonuclease activity that does not require metal ions and preferentially cleaves unstructured single-stranded RNA, while structured RNA substrates are largely resistant to cleavage. Functional analysis indicates that the stalk domain of NP plays a central role in coordinating RNA binding, oligomerization, and access to the nuclease-active site, thereby influencing whether an RNA molecule is protected or degraded. Finally, we identified a small-molecule compound that interferes with both RNA binding and nuclease activity by targeting a conserved functional region of nairovirus NP. Together, these results reveal an expanded functional repertoire of nairovirus NPs and suggest that NP-mediated RNA discrimination may contribute to viral replication. Our findings also support the feasibility of targeting NP for the development of antiviral drugs against emerging nairoviruses.<\/jats:p>","DOI":"10.1073\/pnas.2602311123","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:03:18Z","timestamp":1783447398000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Structural insights into the nairovirus nucleoprotein endonuclease activity"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7257-5992","authenticated-orcid":false,"given":"Zan","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University","place":["Shenzhen, 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Li Crystal structure of full-length TcTV1 nucleoprotein. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9UP8\/pdb. Deposited 27 April 2025.","DOI":"10.2210\/pdb9up8\/pdb"},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","unstructured":"Z. Li Crystal structure of the TcTV1 nucleoprotein\u2013nucleic acid complex. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9UP1\/pdb. Deposited 27 April 2025.","DOI":"10.2210\/pdb9up1\/pdb"},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","unstructured":"Z. Li Crystal structure of the TcTV1 nucleoprotein head domain. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9UOM\/pdb. Deposited 26 April 2025.","DOI":"10.2210\/pdb9uom\/pdb"},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","unstructured":"Z. Li Crystal structure of the selenomethionine-labeled TcTV1 nucleoprotein head domain. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9UON\/pdb. Deposited 26 April 2025.","DOI":"10.2210\/pdb9uon\/pdb"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2602311123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:06:26Z","timestamp":1783447586000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2602311123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":56,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2026,7,14]]}},"alternative-id":["10.1073\/pnas.2602311123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2602311123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"2026-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2602311123"}}