{"doi":"10.1093/nar/gkaf156","title":"Structural investigation of an RNA device that regulates <i>PD-1</i> expression in mammalian cells","abstract":"Synthetic RNA devices are engineered to control gene expression and offer great potential in both biotechnology and clinical applications. Here, we present multidisciplinary structural and biochemical data for a tetracycline (Tc)-responsive RNA device (D43) in both ligand-free and bound states, providing a structure-dynamical basis for signal transmission. Activation of self-cleavage is achieved via ligand-induced conformational and dynamical changes that stabilize the elongated bridging helix harboring the communication module, which drives proper coordination of the catalytic residues. We then show the utility of CRISPR-integrated D43 in EL4 lymphocytes to regulate programmed cell death protein 1 (PD-1), a key receptor of immune checkpoints. Treatment of these cells with Tc showed a dose-dependent reduction in PD-1 by immunostaining and a decrease in messenger RNA levels by quantitative PCR as compared with wild type. PD-1 expression was recoverable upon removal of Tc. These results provide mechanistic insight into RNA devices with potential for cancer immunotherapy or other applications.","journal":"Nucleic Acids Research","year":2025,"id":543388,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"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":634061,"name":"Justin C. Deme","orcid":"0000-0001-8811-9871","position":1,"is_corresponding":false},{"id":1433044,"name":"Vibha Dwivedi","orcid":"0000-0003-4676-0139","position":2,"is_corresponding":false},{"id":715738,"name":"Yun-Tzai Lee","orcid":"0000-0001-8123-6207","position":3,"is_corresponding":false},{"id":978866,"name":"Hyun Kyung Lee","orcid":"0000-0001-5295-1834","position":4,"is_corresponding":false},{"id":715737,"name":"Ping Yu","orcid":"0000-0001-9369-8046","position":5,"is_corresponding":false},{"id":1433443,"name":"Szu-Yun Chen","orcid":null,"position":6,"is_corresponding":false},{"id":228421,"name":"Lixin Fan","orcid":"0000-0002-9232-9262","position":7,"is_corresponding":false},{"id":445158,"name":"Maximilia Frazão de Souza Degenhardt","orcid":"0000-0003-4522-377X","position":8,"is_corresponding":false},{"id":260578,"name":"Raj Chari","orcid":"0000-0002-2216-313X","position":9,"is_corresponding":false},{"id":309027,"name":"Howard A. Young","orcid":"0000-0002-3118-5111","position":10,"is_corresponding":false},{"id":634063,"name":"Susan M. Lea","orcid":"0000-0001-9287-8053","position":11,"is_corresponding":false},{"id":376824,"name":"Yun‐Xing Wang","orcid":"0000-0002-2175-0148","position":12,"is_corresponding":false},{"id":393440,"name":"Jason R. Stagno","orcid":"0000-0002-6464-7829","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:53:04.088079Z","pmid":"40071935","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":[]}