{"doi":"10.1093/nar/gkaf246","title":"LIET model: capturing the kinetics of RNA polymerase from loading to termination","abstract":"Transcription by RNA polymerases is an exquisitely regulated step of the central dogma. Transcription is the primary determinant of cell-state, and most cellular perturbations impact transcription by altering polymerase activity. Thus, detecting changes in polymerase activity yields insight into most cellular processes. Nascent run-on sequencing provides a direct readout of polymerase activity, but no tools exist to model all aspects of this activity at genes. We focus on RNA polymerase II-responsible for transcribing protein-coding genes. We present the first model to capture the complete process of gene transcription. For individual genes, this model parameterizes each distinct stage of transcription-loading, initiation, elongation, and termination, hence LIET-in a biologically interpretable Bayesian mixture, which is applied to nascent run-on data. Our improved modeling of loading/initiation demonstrates these stages are characteristically different between sense and antisense strands. Applying LIET to 24 human cell-types, our analysis indicates the position of dissociation (the last step of termination) appears to be highly consistent, indicative of a tightly regulated process. Furthermore, by applying LIET to perturbation experiments, we demonstrate its ability to detect specific changes in pausing (5' end), strand-bias, and dissociation location (3' end)-opening the door to differential assessment of transcription at individual stages of individual genes.","journal":"Nucleic Acids Research","year":2025,"id":538166,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"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":0.9518,"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":1425176,"name":"Georgia E F Barone","orcid":null,"position":1,"is_corresponding":false},{"id":923467,"name":"Hope A. Townsend","orcid":"0009-0001-5998-3369","position":2,"is_corresponding":false},{"id":557260,"name":"Rutendo F. Sigauke","orcid":"0000-0001-5882-4377","position":3,"is_corresponding":false},{"id":355216,"name":"Mary Allen","orcid":"0000-0001-8163-0714","position":4,"is_corresponding":false},{"id":28295,"name":"Robin D. Dowell","orcid":"0000-0001-7665-9985","position":5,"is_corresponding":false},{"id":557259,"name":"Jacob T. Stanley","orcid":"0000-0002-5652-727X","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:21.389196Z","pmid":"40226915","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":[]}