{"doi":"10.1101/2023.05.02.539157","title":"Toxic anti-phage defense proteins inhibited by intragenic antitoxin proteins","abstract":"Recombination-promoting nuclease (Rpn) proteins are broadly distributed across bacterial phyla, yet their functions remain unclear. Here we report these proteins are new toxin-antitoxin systems, comprised of genes-within-genes, that combat phage infection. We show the small, highly variable Rpn C -terminal domains (Rpn S ), which are translated separately from the full-length proteins (Rpn L ), directly block the activities of the toxic full-length proteins. The crystal structure of RpnA S revealed a dimerization interface encompassing a helix that can have four amino acid repeats whose number varies widely among strains of the same species. Consistent with strong selection for the variation, we document plasmid-encoded RpnP2 L protects Escherichia coli against certain phages. We propose many more intragenic-encoded proteins that serve regulatory roles remain to be discovered in all organisms. Significance Here we document the function of small genes-within-genes, showing they encode antitoxin proteins that block the functions of the toxic DNA endonuclease proteins encoded by the longer rpn genes. Intriguingly, a sequence present in both long and short protein shows extensive variation in the number of four amino acid repeats. Consistent with a strong selection for the variation, we provide evidence that the Rpn proteins represent a phage defense system.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399215,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":313567,"name":"Xiaofang Jiang","orcid":"0000-0002-0955-8284","position":1,"is_corresponding":false},{"id":291210,"name":"Alison B. Hickman","orcid":"0000-0001-7666-0249","position":2,"is_corresponding":false},{"id":1072199,"name":"Katherine Klier","orcid":null,"position":3,"is_corresponding":false},{"id":808205,"name":"Gabriella I. C. Teodoro","orcid":"0000-0001-9669-5940","position":4,"is_corresponding":false},{"id":291212,"name":"Fred Dyda","orcid":"0000-0003-1689-9041","position":5,"is_corresponding":false},{"id":21271,"name":"Michael T. Laub","orcid":"0000-0002-8288-7607","position":6,"is_corresponding":false},{"id":242351,"name":"Gisela Storz","orcid":"0000-0001-6698-1241","position":7,"is_corresponding":false},{"id":864547,"name":"Aoshu Zhong","orcid":"0000-0002-5793-3990","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:51.724387Z","pmid":"37425788","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":[]}