{"doi":"10.1038/s41564-024-01664-3","title":"tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum","abstract":"Abstract Plasmodium falciparum artemisinin (ART) resistance is driven by mutations in kelch-like protein 13 (PfK13). Quiescence, a key aspect of resistance, may also be regulated by a yet unidentified epigenetic pathway. Transfer RNA modification reprogramming and codon bias translation is a conserved epitranscriptomic translational control mechanism that allows cells to rapidly respond to stress. We report a role for this mechanism in ART-resistant parasites by combining tRNA modification, proteomic and codon usage analyses in ring-stage ART-sensitive and ART-resistant parasites in response to drug. Post-drug, ART-resistant parasites differentially hypomodify mcm 5 s 2 U on tRNA and possess a subset of proteins, including PfK13, that are regulated by Lys codon-biased translation. Conditional knockdown of the terminal s 2 U thiouridylase, PfMnmA, in an ART-sensitive parasite background led to increased ART survival, suggesting that hypomodification can alter the parasite ART response. This study describes an epitranscriptomic pathway via tRNA s 2 U reprogramming that ART-resistant parasites may employ to survive ART-induced stress.","journal":"Nature Microbiology","year":2024,"id":421328,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"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":1213493,"name":"Ameya Sinha","orcid":"0000-0001-7959-075X","position":1,"is_corresponding":false},{"id":1213494,"name":"Talia S. Bloxham","orcid":"0009-0002-8613-0457","position":2,"is_corresponding":false},{"id":884747,"name":"Laura M. Hagenah","orcid":"0000-0001-8258-6823","position":3,"is_corresponding":false},{"id":813280,"name":"Guangxin Sun","orcid":"0000-0001-6036-8809","position":4,"is_corresponding":false},{"id":798595,"name":"Peter R. Preiser","orcid":null,"position":5,"is_corresponding":false},{"id":289582,"name":"Peter C. Dedon","orcid":"0000-0003-0011-3067","position":6,"is_corresponding":false},{"id":107758,"name":"David A. Fidock","orcid":"0000-0001-6753-8938","position":7,"is_corresponding":false},{"id":626326,"name":"Jennifer L. Small-Saunders","orcid":"0000-0001-6064-2249","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T01:57:36.298171Z","pmid":"38632343","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":[]}