{"doi":"10.1016/j.jbc.2024.107951","title":"Knotty is nice: Metabolite binding and RNA-mediated gene regulation by the preQ1 riboswitch family","abstract":"Riboswitches sense specific cellular metabolites, leading to messenger RNA conformational changes that regulate downstream genes. Here, we review the three known prequeosine 1 (preQ 1 ) riboswitch classes, which encompass five gene-regulatory motifs derived from distinct consensus models of folded RNA pseudoknots. Structural and functional analyses reveal multiple gene-regulation strategies ranging from partial occlusion of the ribosome-binding Shine-Dalgarno sequence (SDS), SDS sequestration driven by kinetic or thermodynamic folding pathways, direct preQ 1 recognition by the SDS, and complete SDS burial with in the riboswitch architecture. Family members can also induce elemental transcriptional pausing, which depends on ligand-mediated pseudoknot formation. Accordingly, preQ 1 family members provide insight into a wide range of gene-regulatory tactics as well as a diverse repertoire of chemical approaches used to recognize the preQ 1 metabolite. From a broader perspective, future challenges for the field will include the identification of new riboswitches in mRNAs that do not possess an SDS or those that induce ligand-dependent transcriptional pausing. When choosing an antibacterial target, the field must also consider how well a riboswitch accommodates mutations. Investigation of riboswitches in their natural context will also be critical to elucidate how RNA-mediated gene regulation influences organism fitness, thus providing a firm foundation for antibiotic development.","journal":"Journal of Biological Chemistry","year":2024,"id":458689,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1285463,"name":"Coleman Goenner","orcid":null,"position":1,"is_corresponding":false},{"id":1284948,"name":"Matthew Law","orcid":"0000-0002-5048-4256","position":2,"is_corresponding":false},{"id":467929,"name":"Griffin M. Schroeder","orcid":"0000-0001-6354-752X","position":3,"is_corresponding":false},{"id":1150939,"name":"Yoshita Srivastava","orcid":"0000-0001-9091-9851","position":4,"is_corresponding":false},{"id":458608,"name":"Jermaine L. Jenkins","orcid":"0000-0003-2548-3275","position":5,"is_corresponding":false},{"id":467934,"name":"Joseph E. Wedekind","orcid":"0000-0002-4269-4229","position":6,"is_corresponding":false},{"id":1074463,"name":"Daniil Kiliushik","orcid":"0000-0003-3055-5122","position":0,"is_corresponding":true}],"reference_count":141,"raw_metadata":null,"created_at":"2026-07-19T02:03:50.608887Z","pmid":"39486689","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":[]}