{"doi":"10.1021/jacs.3c11158","title":"Unusual Base Pair between Two 2-Thiouridines and Its Implication for Nonenzymatic RNA Copying","abstract":"High Resolution Image Download MS PowerPoint Slide 2-Thiouridine (s 2 U) is a nucleobase modification that confers enhanced efficiency and fidelity both on modern tRNA codon translation and on nonenzymatic and ribozyme-catalyzed RNA copying. We have discovered an unusual base pair between two 2-thiouridines that stabilizes an RNA duplex to a degree that is comparable to that of a native A:U base pair. High-resolution crystal structures indicate similar base-pairing geometry and stacking interactions in duplexes containing s 2 U:s 2 U compared to those with U:U pairs. Notably, the C═O···H–N hydrogen bond in the U:U pair is replaced with a C═S···H–N hydrogen bond in the s 2 U:s 2 U base pair. The thermodynamic stability of the s 2 U:s 2 U base pair suggested that this self-pairing might lead to an increased error frequency during nonenzymatic RNA copying. However, competition experiments show that s 2 U:s 2 U base-pairing induces only a low level of misincorporation during nonenzymatic RNA template copying because the correct A:s 2 U base pair outcompetes the slightly weaker s 2 U:s 2 U base pair. In addition, even if an s 2 U is incorrectly incorporated, the addition of the next base is greatly hindered. This strong stalling effect would further increase the effective fidelity of nonenzymatic RNA copying with s 2 U. Our findings suggest that s 2 U may enhance the rate and extent of nonenzymatic copying with only a minimal cost in fidelity.","journal":"Journal of the American Chemical Society","year":2024,"id":452682,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"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":724622,"name":"Ziyuan Fang","orcid":"0000-0001-8679-6633","position":1,"is_corresponding":false},{"id":407630,"name":"Seohyun Chris Kim","orcid":"0000-0002-2230-1774","position":2,"is_corresponding":false},{"id":1274884,"name":"Derek K. O’Flaherty","orcid":"0000-0003-3693-6380","position":3,"is_corresponding":false},{"id":1274885,"name":"Xiwen Jia","orcid":"0000-0001-9094-9882","position":4,"is_corresponding":false},{"id":1274886,"name":"Talbot B. Stone","orcid":"0009-0000-7843-5678","position":5,"is_corresponding":false},{"id":1274887,"name":"Lijun Zhou","orcid":"0000-0002-0393-4787","position":6,"is_corresponding":false},{"id":366275,"name":"Jack W. Szostak","orcid":"0000-0003-4131-1203","position":7,"is_corresponding":false},{"id":1274883,"name":"Dian Ding","orcid":"0000-0001-9046-7816","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:02:54.415477Z","pmid":"38293747","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":[]}