{"doi":"10.1101/2020.12.17.423219","title":"Poly(ADP-ribose) potentiates ZAP antiviral activity","abstract":"Abstract Zinc-finger antiviral protein (ZAP), also known as poly(ADP-ribose) polymerase 13 (PARP13), is an antiviral factor that selectively targets viral RNA for degradation. ZAP is active against both DNA and RNA viruses, including important human pathogens such as hepatitis B virus and type 1 human immunodeficiency virus (HIV-1). ZAP selectively binds CpG dinucleotides through its N-terminal RNA-binding domain, which consists of four zinc fingers. ZAP also contains a central region that consists of a fifth zinc finger and two WWE domains. Through structural and biochemical studies, we found that the fifth zinc finger and tandem WWEs of ZAP combine into a single integrated domain that binds to poly(ADP-ribose) (PAR), a cellular polynucleotide. PAR binding is mediated by the second WWE module of ZAP and likely involves specific recognition of iso (ADP-ribose), a repeating structural unit of PAR. Mutation of the putative iso (ADP-ribose) binding site in ZAP abrogates the interaction in vitro and diminishes ZAP activity against a CpG-rich HIV-1 reporter virus. In cells, PAR facilitates formation of non-membranous sub-cellular compartments such as DNA repair foci, spindle poles and cytosolic RNA stress granules. Our results suggest that ZAP-mediated viral mRNA degradation is facilitated by PAR, and provides a biophysical rationale for the reported association of ZAP with RNA stress granules.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123189,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":565881,"name":"Klaudia Braczyk","orcid":"0000-0003-3574-8644","position":1,"is_corresponding":false},{"id":565882,"name":"Daniel Gonçalves-Carneiro","orcid":"0000-0002-9333-1540","position":2,"is_corresponding":false},{"id":565883,"name":"Daria M. Dawidziak","orcid":"0000-0001-7468-5346","position":3,"is_corresponding":false},{"id":565884,"name":"Katarzyna Zawada","orcid":"0000-0002-4065-9841","position":4,"is_corresponding":false},{"id":565885,"name":"Heley Ong","orcid":"0000-0002-9651-3892","position":5,"is_corresponding":false},{"id":565886,"name":"Yueping Wan","orcid":"0000-0002-1025-9222","position":6,"is_corresponding":false},{"id":562724,"name":"Kaneil K. Zadrozny","orcid":null,"position":7,"is_corresponding":false},{"id":255582,"name":"Barbie K. Ganser‐Pornillos","orcid":"0000-0001-6453-3891","position":8,"is_corresponding":false},{"id":16992,"name":"Paul D. Bieniasz","orcid":"0000-0002-2368-3719","position":9,"is_corresponding":false},{"id":255584,"name":"Owen Pornillos","orcid":"0000-0001-9056-5002","position":10,"is_corresponding":false},{"id":565880,"name":"Guangai Xue","orcid":"0009-0009-9307-2719","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:14:59.547352Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}