{"doi":"10.1073/pnas.2405999121","title":"A novel <i>N</i> 4, <i>N</i> 4-dimethylcytidine in the archaeal ribosome enhances hyperthermophily","abstract":"Ribosome structure and activity are challenged at high temperatures, often demanding modifications to ribosomal RNAs (rRNAs) to retain translation fidelity. LC-MS/MS, bisulfite-sequencing, and high-resolution cryo-EM structures of the archaeal ribosome identified an RNA modification, N 4, N 4-dimethylcytidine (m 4 2 C), at the universally conserved C918 in the 16S rRNA helix 31 loop. Here, we characterize and structurally resolve a class of RNA methyltransferase that generates m 4 2 C whose function is critical for hyperthermophilic growth. m 4 2 C is synthesized by the activity of a unique family of RNA methyltransferase containing a Rossman-fold that targets only intact ribosomes. The phylogenetic distribution of the newly identified m 4 2 C synthase family implies that m 4 2 C is biologically relevant in each domain. Resistance of m 4 2 C to bisulfite-driven deamination suggests that efforts to capture m 5 C profiles via bisulfite sequencing are also capturing m 4 2 C.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":469636,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"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":240055,"name":"Nan Dai","orcid":"0000-0003-3268-1835","position":1,"is_corresponding":false},{"id":369419,"name":"Eric J. Wolf","orcid":"0009-0005-7262-2364","position":2,"is_corresponding":false},{"id":232485,"name":"Ryan T. Fuchs","orcid":"0000-0001-8238-6442","position":3,"is_corresponding":false},{"id":391237,"name":"P Shing Ho","orcid":"0000-0002-8082-4311","position":4,"is_corresponding":false},{"id":1237000,"name":"Victoria Talbott","orcid":"0009-0000-6078-997X","position":5,"is_corresponding":false},{"id":1237433,"name":"Liam Elkins","orcid":null,"position":6,"is_corresponding":false},{"id":346162,"name":"Yueh-Lin Tsai","orcid":null,"position":7,"is_corresponding":false},{"id":1237434,"name":"Jackson Schiltz","orcid":null,"position":8,"is_corresponding":false},{"id":436203,"name":"Hallie P. Febvre","orcid":"0009-0004-9443-616X","position":9,"is_corresponding":false},{"id":391880,"name":"Ryan S. Czarny","orcid":null,"position":10,"is_corresponding":false},{"id":232486,"name":"G. Brett Robb","orcid":"0000-0002-2382-2256","position":11,"is_corresponding":false},{"id":121504,"name":"Ivan R Corrêa","orcid":"0000-0002-3169-6878","position":12,"is_corresponding":false},{"id":232492,"name":"Thomas J. Santangelo","orcid":"0000-0003-4559-3244","position":13,"is_corresponding":false},{"id":722366,"name":"Kristin Scott","orcid":"0000-0002-3398-3184","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:05:32.241298Z","pmid":"39471227","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":[]}