{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T10:16:57Z","timestamp":1787912217323,"version":"build-2784847793"},"reference-count":54,"publisher":"Wiley","issue":"48","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220776\/Z\/20\/Z"],"award-info":[{"award-number":["220776\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223107\/Z\/21\/Z"],"award-info":[{"award-number":["223107\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/Y000307\/1"],"award-info":[{"award-number":["BB\/Y000307\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Flavivirus subgenomic RNAs (sfRNAs) antagonise antiviral defences, yet how sfRNAs are organized and maintained in cells remains poorly understood. Here we identify ubiquitin C\u2010terminal hydrolase L3 (UCHL3) as a post\u2010translational regulator of flavivirus sfRNA stability and function. Using activity\u2010based protein profiling during ZIKV and DENV infections, we discovered that UCHL3 is activated upon flavivirus infection. CRISPR\u2010Cas9 knockout of UCHL3 significantly impaired viral replication and reduced viral protein expression across multiple cell models; reconstitution with wild\u2010type UCHL3 rescued these defects, whereas a catalytically inactive mutant (C95A) failed to restore replication, confirming the requirement for deubiquitylase activity. Through a proximity\u2010biotinylation sfRNA\u2010interactome capture assay, we show that UCHL3 physically interacts with sfRNA complexes. Importantly, UCHL3 deletion accelerates RNase L activation, causing enhanced sfRNA relocalization from protective P\u2010bodies to PABPC1\u2010positive RNase L\u2010induced bodies (RLBs), resulting in viral RNA decay. RNase L knockdown restores viral replication in UCHL3\u2010deficient cells, confirming RNase L\u2010dependent antiviral effects. This pro\u2010viral effect of UCHL3 operates through interferon\u2010independent mechanisms, as replication defects persist despite exogenous interferon treatment. This work therefore identifies UCHL3 as a regulator of sfRNA fate between pro\u2010viral and antiviral RNA condensates, identifying a post\u2010translational mechanism governing viral RNA stability and a potential therapeutic target for flavivirus infections.<\/jats:p>","DOI":"10.1002\/advs.202521781","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:40:27Z","timestamp":1780472427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["UCHL3 Regulates Subgenomic Flaviviral RNA Condensates to Promote Virus Propagation"],"prefix":"10.1002","volume":"13","author":[{"given":"Oscar","family":"Trejo\u2010Cerro","sequence":"first","affiliation":[{"name":"Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Beekmayer\u2010Dhillon","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi Wen","family":"Teo","sequence":"additional","affiliation":[{"name":"HKU\u2010Pasteur research pole School of Public Health University of Hong Kong  Hong Kong SAR China"},{"name":"Current address: Department of Biochemistry University of Illinois Urbana\u2010Champaign  Urbana IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Siu","sequence":"additional","affiliation":[{"name":"HKU\u2010Pasteur research pole School of Public Health University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology and Li Ka Shing Institute of Health Sciences Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate J.","family":"Heesom","sequence":"additional","affiliation":[{"name":"Proteomics Facility University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e1n","family":"Pinto\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Translational Ubiquitomics Laboratory Nuffield Department of Medicine CAMS Oxford Institute and Centre for Medicines Discovery University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-5366","authenticated-orcid":false,"given":"Sumana","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010virology\u2010092623\u2010110537"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.262164"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2018.09.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02604-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.10.007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add8095"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01954-23"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1905617116"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114694"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02070-1"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2021.01.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.01.025"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.11.005"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.10.027"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01035-8"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220839"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.015"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2023.08.013"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150626"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1628-8"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-0181-3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2023.0011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38377-w"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","unstructured":"A.Banducci\u2010Karp Remodelled Cholesteryl Ester Enriched Lipid Droplets Fuel Flavivirus Morphogenesis(2025) Preprint athttps:\/\/doi.org\/10.1101\/2025.06.07.658178(2025).","DOI":"10.1101\/2025.06.07.658178"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-025-01940-w"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19028-w"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009658"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4601"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.07.027"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.07.029"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.011638"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2026.116924"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2026.117028"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.7"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2021.03.005"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.09.041"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02791-14"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1770"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.12.020"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.017"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050835"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.229252"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107859"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100173"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.005"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012766"},{"key":"e_1_2_9_48_1","unstructured":"C.Mazeaud \u201cZika Virus Remodels and Hijacks IGF2BP2 ribonucleoprotein Complex to Promote Viral Replication Organelle Biogenesis \u201dPreprint athttps:\/\/doi.org\/10.7554\/eLife.94347.1(2024)."},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a037093"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1519657113"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf840"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3437"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.10.011"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.365312"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25687"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202521781","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202521781","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202521781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:26:34Z","timestamp":1787909194000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202521781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":54,"journal-issue":{"issue":"48","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/advs.202521781"],"URL":"https:\/\/doi.org\/10.1002\/advs.202521781","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"2025-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21781"}}