{"doi":"10.1016/j.bpj.2022.02.004","title":"Modeling bursty transcription and splicing with the chemical master equation","abstract":"Splicing cascades that alter gene products post-transcriptionally also affect expression dynamics. We study a class of processes and associated distributions that emerge from models of bursty promoters coupled to directed acyclic graphs of splicing. These solutions provide full time-dependent joint distributions for an arbitrary number of species with general noise behaviors and transient phenomena, offering qualitative and quantitative insights about how splicing can regulate expression dynamics. Finally, we derive a set of quantitative constraints on the minimum complexity necessary to reproduce gene coexpression patterns using synchronized burst models. We validate these findings by analyzing long-read sequencing data, where we find evidence of expression patterns largely consistent with these constraints. SIGNIFICANCE Understanding mRNA transcription requires an arsenal of tractable and versatile Markov models. Bursty transcription is ubiquitous in mammalian cells; however, only a few such systems have been mathematically characterized. We expand their scope and present full probabilistic solutions for bursty transcription at multiple, potentially synchronized, gene loci, coupled to arbitrary directed acyclic graphs of splicing. We use these general results to derive quantitative constraints on transcript count correlations, motivate physically plausible classes of burst models, and validate the constraints using single-cell sequencing data.","journal":"Biophysical Journal","year":2022,"id":246000,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242923,"name":"Lior Pachter","orcid":"0000-0002-9164-6231","position":1,"is_corresponding":false},{"id":282802,"name":"Gennady Gorin","orcid":"0000-0001-6097-2029","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35143775","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":[]}