{"doi":"10.1101/2024.07.05.602228","title":"Toxic Small Alarmone Synthetase FaRel2 inhibits translation by pyrophosphorylating tRNA <sup>Gly</sup> and tRNA <sup>Thr</sup>","abstract":"Abstract Translation-targeting toxic Small Alarmone Synthetases (toxSAS) are effectors of bacterial Toxin-Antitoxin systems that pyrophosphorylate the 3’-CCA end of tRNA to prevent aminoacylation. toxSAS are implicated in antiphage immunity: phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNA Gly and tRNA Thr . The 1 st , 2 nd , 4 th and 5 th base pairs the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRel SJ46 differ in tRNA specificity from FaRel2, and rationalise this through structural modelling: while the universal 3’-CCA end slots into a highly conserved CCA recognition groove, the acceptor stem recognition region is variable across toxSAS diversity. As phages use tRNA isoacceptors to overcome tRNA-targeting defences, we hypothesise that highly evolvable modular tRNA recognition allows for the escape of viral countermeasures through tRNA substrate specificity switching.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491344,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1336950,"name":"Masaki Takegawa","orcid":null,"position":1,"is_corresponding":false},{"id":1162418,"name":"Takayuki Ohira","orcid":"0000-0002-1487-1312","position":2,"is_corresponding":false},{"id":351891,"name":"Egor A. Syroegin","orcid":"0000-0003-2753-3950","position":3,"is_corresponding":false},{"id":628878,"name":"Gemma C. Atkinson","orcid":"0000-0002-4861-4584","position":4,"is_corresponding":false},{"id":1336621,"name":"Marcus Johansson","orcid":"0000-0001-7117-7426","position":5,"is_corresponding":false},{"id":351892,"name":"Yury S. Polikanov","orcid":"0000-0002-5064-0327","position":6,"is_corresponding":false},{"id":1336622,"name":"Abel García-Pino","orcid":"0000-0002-0634-0300","position":7,"is_corresponding":false},{"id":236036,"name":"Tsutomu Suzuki","orcid":"0000-0002-9731-1731","position":8,"is_corresponding":false},{"id":811322,"name":"Vasili Hauryliuk","orcid":"0000-0003-2389-5057","position":9,"is_corresponding":false},{"id":882221,"name":"Tatsuaki Kurata","orcid":"0000-0001-5986-7141","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:08:41.211111Z","pmid":"39005314","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":[]}