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A novel 119\u2010amino\u2010acid protein, NLRP12\u2010119aa is identified, encoded by the circular RNA circNLRP12, that effectively disrupts the formation of rhabdovirus RNP complexes through two distinct mechanisms and significantly reduces their replication. NLRP12\u2010119aa exhibits a strong affinity for the conserved 18\u2010nucleotide sequence at the start of the leader RNA of rhabdoviruses VSV, SCRV, and RABV, outcompeting their native N protein interactions, thereby disrupting the assembly of RNP complexes and inhibiting viral replication. NLRP12\u2010119aa exerts anti\u2010rhabdoviral effects by directly binding to the viral N protein, leading to its destabilization and accelerated degradation, and consequently hindering the formation of the viral RNP complex. To assess the therapeutic potential of circNLRP12 against rhabdovirus infections, a zebrafish model of VSV infection is established and noted a substantial reduction in viral load after\u2010treatment with circNLRP12, as well as the recovery of spleen's to a normalized state from its previously enlarged and hemorrhagic state. Collectively, these findings elucidate a novel dual anti\u2010RNP assembly strategy mediated by NLRP12\u2010119aa, offering valuable insights for further exploration and clinical management of rhabdoviral infections.<\/jats:p>","DOI":"10.1002\/advs.202409953","type":"journal-article","created":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T12:39:53Z","timestamp":1735994393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Protein NLRP12\u2010119aa that Prevents Rhabdovirus Replication by Disrupting the RNP Complex Formation"],"prefix":"10.1002","volume":"12","author":[{"given":"Weiwei","family":"Zheng","sequence":"first","affiliation":[{"name":"Laboratory of Fish Molecular Immunology College of Fisheries and Life Science Shanghai Ocean University  Shanghai 201306 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Fish Molecular Immunology College of Fisheries and Life Science Shanghai Ocean University  Shanghai 201306 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Fish Molecular Immunology College of Fisheries and Life Science Shanghai Ocean University  Shanghai 201306 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Laboratory of Fish Molecular Immunology College of Fisheries and Life Science Shanghai Ocean University  Shanghai 201306 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Fish Molecular Immunology College of Fisheries and Life Science Shanghai Ocean University  Shanghai 201306 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3606-8069","authenticated-orcid":false,"given":"Tianjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Fish Molecular Immunology College of Fisheries and Life Science Shanghai Ocean University  Shanghai 201306 China"},{"name":"Laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center  Qingdao 266200 China"},{"name":"Marine Biomedical Science and Technology Innovation Platform of Lin\u2010gang Special Area  Shanghai 201306 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,4]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12090959"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2010.02.322"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387040-7.00001-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2004.03.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2018.11"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/01652176.2017.1343516"},{"key":"e_1_2_9_4_3","first-page":"55","volume":"5","author":"Barecha C. 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