{"doi":"10.1016/j.celrep.2023.112111","title":"Promiscuous splicing-derived hairpins are dominant substrates of tailing-mediated defense of miRNA biogenesis in mammals","abstract":"Canonical microRNA (miRNA) hairpins are processed by the RNase III enzymes Drosha and Dicer into ∼22 nt RNAs loaded into an Argonaute (Ago) effector. In addition, splicing generates numerous intronic hairpins that bypass Drosha (mirtrons) to yield mature miRNAs. Here, we identify hundreds of previously unannotated, splicing-derived hairpins in intermediate-length (∼50-100 nt) but not small (20-30 nt) RNA data. Since we originally defined mirtrons from small RNA duplexes, we term this larger set as structured splicing-derived RNAs (ssdRNAs). These associate with Dicer and/or Ago complexes, but generally accumulate modestly and are poorly conserved. We propose they contaminate the canonical miRNA pathway, which consequently requires defense against the siege of splicing-derived substrates. Accordingly, ssdRNAs/mirtrons comprise dominant hairpin substrates for 3' tailing by multiple terminal nucleotidyltransferases, notably TUT4/7 and TENT2. Overall, the rampant proliferation of young mammalian mirtrons/ssdRNAs, coupled with an inhibitory molecular defense, comprises a Red Queen's race of intragenomic conflict.","journal":"Cell Reports","year":2023,"id":347446,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":252897,"name":"David Jee","orcid":null,"position":1,"is_corresponding":false},{"id":1089354,"name":"Sid Srivastava","orcid":null,"position":2,"is_corresponding":false},{"id":294366,"name":"Acong Yang","orcid":"0000-0002-1279-566X","position":3,"is_corresponding":false},{"id":1088911,"name":"Abhinav Ramidi","orcid":"0009-0008-8437-7783","position":4,"is_corresponding":false},{"id":348825,"name":"Renfu Shang","orcid":"0000-0002-3361-3036","position":5,"is_corresponding":false},{"id":1089355,"name":"Diane Bortolamiol-Bécet","orcid":null,"position":6,"is_corresponding":false},{"id":1088912,"name":"Sébastien Pfeffer","orcid":"0000-0002-8458-348X","position":7,"is_corresponding":false},{"id":294368,"name":"Shuo Gu","orcid":"0000-0002-7924-5363","position":8,"is_corresponding":false},{"id":41931,"name":"Jiayu Wen","orcid":"0000-0003-1249-6456","position":9,"is_corresponding":false},{"id":182940,"name":"Eric C Lai","orcid":"0000-0002-8432-5851","position":10,"is_corresponding":false},{"id":348469,"name":"Seungjae Lee","orcid":"0000-0001-5626-9656","position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":null,"created_at":"2026-07-19T01:11:57.720122Z","pmid":"36800291","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":[]}