{"doi":"10.1101/2021.06.03.446796","title":"Ring Finger Protein 213 Assembles into a Sensor for ISGylated Proteins with Antimicrobial Activity","abstract":"ABSTRACT ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we used a viral-like particle trapping technology to identify ISG15-binding proteins and discovered Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly-characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We found that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We showed that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1 (HSV-1), human respiratory syncytial virus (RSV) and coxsackievirus B3 (CVB3), and we observed a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide novel molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216133,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":630589,"name":"Lia Martina","orcid":"0000-0001-8168-0332","position":1,"is_corresponding":false},{"id":630590,"name":"Caroline Asselman","orcid":"0000-0002-0007-5091","position":2,"is_corresponding":false},{"id":631532,"name":"Heidi Repo","orcid":null,"position":3,"is_corresponding":false},{"id":254484,"name":"Yifeng Zhang","orcid":"0000-0002-7348-0223","position":4,"is_corresponding":false},{"id":630591,"name":"Koen Sedeyn","orcid":"0000-0002-1303-1629","position":5,"is_corresponding":false},{"id":631533,"name":"George D. 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