{"doi":"10.1021/jacs.0c05635","title":"RNA-Catalyzed Cross-Chiral Polymerization of RNA","abstract":"Biology relies almost exclusively on homochiral building blocks to drive the processes of life. Yet cross-chiral interactions can occur between macromolecules of the opposite handedness, including a previously described polymerase ribozyme that catalyzes the template-directed synthesis of enantio-RNA. The present study sought to optimize and generalize this activity, employing in vitro evolution to select cross-chiral polymerases that use either mono- or trinucleotide substrates that are activated as the 5′-triphosphate. There was only modest improvement of the former activity, but dramatic improvement of the latter, which enables the trinucleotide polymerase to react 102–103-fold faster than its ancestor and to accept substrates with all possible sequence combinations. The evolved ribozyme can assemble long RNAs from a mixture of trinucleotide building blocks, including a two-fragment form of the ancestral polymerase ribozyme. Further improvement of this activity could enable the generalized cross-chiral replication of RNA, which would establish a new paradigm for the chemical basis of Darwinian evolution.","journal":"Journal of the American Chemical Society","year":2020,"id":99366,"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":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":479667,"name":"Jonathan T. Sczepanski","orcid":"0000-0002-9275-2597","position":1,"is_corresponding":false},{"id":489695,"name":"Eric R. Murtfeldt","orcid":null,"position":2,"is_corresponding":false},{"id":266629,"name":"Gerald F. Joyce","orcid":"0000-0003-0603-2874","position":3,"is_corresponding":false},{"id":269140,"name":"Katrina F. Tjhung","orcid":null,"position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T22:37:35.547042Z","pmid":"32805113","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":[]}