{"doi":"10.1101/2021.12.21.472683","title":"An Atypical RNA Quadruplex Marks RNAs as Vectors for Gene Silencing","abstract":"The addition of poly(UG) (\"pUG\") repeats to 3' termini of mRNAs drives gene silencing and trans-generational epigenetic inheritance in the metazoan C. elegans. pUG tails promote silencing by recruiting an RNA-dependent RNA Polymerase (RdRP) that synthesizes small interfering (si)RNAs. Here we show that active pUG tails require a minimum of 11.5 repeats and adopt a quadruplex (G4)2 structure we term the pUG fold. The pUG fold differs from known G4s in that it has a left-handed backbone similar to Z-RNA, no consecutive guanosines in its sequence, and three G quartets and one U quartet stacked non-sequentially. Its biological importance is emphasized by our observations that porphyrin molecules bind to the pUG fold and inhibit both gene silencing and binding of RdRP. Moreover, specific N7-deaza RNA substitutions that do not adopt the pUG fold neither bind RdRP nor induce RNA silencing. These data define the pUG fold as a previously unrecognized RNA secondary structure motif that drives gene silencing. The pUG fold can also form internally within larger RNA molecules. Approximately 20,000 pUG-fold sequences are found in non-coding regions of human RNAs, suggesting the fold likely has biological roles beyond gene silencing.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":217010,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255519,"name":"Jenny Yan","orcid":"0000-0001-9978-0905","position":1,"is_corresponding":false},{"id":334782,"name":"Yuichiro Nomura","orcid":"0000-0002-8275-4468","position":2,"is_corresponding":false},{"id":483411,"name":"Cristian A. Escobar","orcid":"0000-0002-4607-2996","position":3,"is_corresponding":false},{"id":813502,"name":"Riley J. Petersen","orcid":"0000-0003-3598-0507","position":4,"is_corresponding":false},{"id":301266,"name":"C.A. Bingman","orcid":"0000-0002-3073-5089","position":5,"is_corresponding":false},{"id":346055,"name":"Marco Tonelli","orcid":"0000-0002-7700-5745","position":6,"is_corresponding":false},{"id":334780,"name":"Eric Montemayor","orcid":"0000-0001-7883-7706","position":7,"is_corresponding":false},{"id":255524,"name":"Scott Kennedy","orcid":"0000-0002-7974-8155","position":8,"is_corresponding":false},{"id":570053,"name":"Samuel E. Butcher","orcid":"0000-0001-6343-6643","position":9,"is_corresponding":false},{"id":813501,"name":"Saeed Roschdi","orcid":"0000-0001-6360-6868","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:53:15.868165Z","pmid":null,"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":[]}