{"doi":"10.1093/nar/gkaf137","title":"A novel L-RNA aptamer to regulate the pUG fold RNA-induced gene expression <i>in vivo</i>","abstract":"G-quadruplex (G4) is a guanine-rich secondary structure found in DNA and RNA involved in various biological roles. Recently, a non-canonical RNA G-quadruplex (rG4), known as poly(UG) (pUG) fold, was discovered in Caenorhabditis elegans. This unique structure was found to induce RNA interference (RNAi) upon recruitment of RNA-dependent RNA polymerase (RdRP), resulting in trans-generational gene silencing. Herein, we develop a novel L-RNA aptamer, L-apt3.1, that binds to the pUG fold. We uncover that L-apt3.1 consists of a parallel rG4 structural motif, and mutagenesis analysis illustrates that the rG4 motif in L-apt3.1 is essential for pUG fold recognition. We show that L-apt3.1 interacts strongly with pUG fold, and notably, it is the first reported aptamer that can bind to pUG fold in vitro. We also demonstrate that L-apt3.1 possesses great biostability in cellular environments and negligible toxicity in vivo. Furthermore, we report that L-apt3.1 can interact with pUG fold in vivo, and with a comparable performance to the G4 ligand, N-methyl mesoporphyrin, in inhibiting gene silencing in C. elegans. Overall, we demonstrate the development of pUG fold-targeting L-RNA aptamer for the first time, and show that this new aptamer tool can be applied to control pUG fold-mediated gene expression in vivo.","journal":"Nucleic Acids Research","year":2025,"id":550282,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":709144,"name":"Dong Cao","orcid":"0000-0002-7253-9043","position":1,"is_corresponding":false},{"id":813502,"name":"Riley J. Petersen","orcid":"0000-0003-3598-0507","position":2,"is_corresponding":false},{"id":570053,"name":"Samuel E. Butcher","orcid":"0000-0001-6343-6643","position":3,"is_corresponding":false},{"id":255524,"name":"Scott Kennedy","orcid":"0000-0002-7974-8155","position":4,"is_corresponding":false},{"id":112352,"name":"Chun Kit Kwok","orcid":"0000-0001-9175-8543","position":5,"is_corresponding":false},{"id":1336985,"name":"Shiau Wei Liew","orcid":"0000-0002-2424-9084","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:54:16.596730Z","pmid":"40057375","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":[]}