{"doi":"10.1073/pnas.1914282117","title":"An RNA polymerase ribozyme that synthesizes its own ancestor","abstract":"The RNA-based organisms from which modern life is thought to have descended would have depended on an RNA polymerase ribozyme to copy functional RNA molecules, including copying the polymerase itself. Such a polymerase must have been capable of copying structured RNAs with high efficiency and high fidelity to maintain genetic information across successive generations. Here the class I RNA polymerase ribozyme was evolved in vitro for the ability to synthesize functional ribozymes, resulting in the markedly improved ability to synthesize complex RNAs using nucleoside 5'-triphosphate (NTP) substrates. The polymerase is descended from the class I ligase, which contains the same catalytic core as the polymerase. The class I ligase can be synthesized by the improved polymerase as three separate RNA strands that assemble to form a functional ligase. The polymerase also can synthesize the complement of each of these three strands. Despite this remarkable level of activity, only a very small fraction of the assembled ligases retain catalytic activity due to the presence of disabling mutations. Thus, the fidelity of RNA polymerization should be considered a major impediment to the construction of a self-sustained, RNA-based evolving system. The propagation of heritable information requires both efficient and accurate synthesis of genetic molecules, a requirement relevant to both laboratory systems and the early history of life on Earth.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":52595,"datarank":0.7335523692332632,"base_score":4.890349128221754,"endowment":4.890349128221754,"self_citation_contribution":0.7335523692332632,"citation_network_contribution":0.0,"self_endowment_contribution":0.7335523692332632,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":132,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"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":266627,"name":"Maxim N. Shokhirev","orcid":"0000-0002-8379-8657","position":1,"is_corresponding":false},{"id":266628,"name":"David P. Horning","orcid":"0000-0003-3357-6092","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":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T20:43:25.742124Z","pmid":"31988127","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":[]}