{"doi":"10.1093/nar/gkag357","title":"Structure and function of IWS1 in transcription elongation","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Transcription elongation by RNA polymerase II is a tightly regulated process that requires coordinated interactions between transcription elongation factors. IWS1 (Interacts with SPT6) has been implicated as a core elongation factor, but its molecular role remains unclear. We show that the intrinsically disordered C-terminal region of IWS1 contains short linear motifs (SLiMs) that multivalently engage the elongation machinery. Using cryo-electron microscopy, we map SLiMs in IWS1 that interact with Pol II subunits RPB1, RPB2, and RPB5, as well as elongation factors DSIF, SPT6, and ELOF1. Functional assays demonstrate that distinct IWS1 SLiMs specify IWS1 recruitment and IWS1-dependent transcription stimulation. IWS1 recruitment to the transcription elongation complex depends on association via the RPB1 jaw and binding of downstream DNA. Transcription elongation stimulation requires interactions with the RPB2 lobe and ELOF1. We identify other transcription elongation factors including ELOA and RECQL5 that bind the RPB1 jaw and demonstrate that IWS1 protects the activated transcription elongation complex from RECQL5 inhibition. We also reveal the binding of the histone reader and IWS1 interactor LEDGF to a transcribed downstream nucleosome. Our findings establish IWS1 as a modular scaffold that helps organize the transcription elongation complex, illustrating how disordered regions regulate transcription elongation.</jats:p>","journal":"Nucleic Acids Research","year":2026,"id":623437,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":623647,"name":"Felix Steinruecke","orcid":"0000-0003-4597-8232","position":1,"is_corresponding":false},{"id":782462,"name":"Sophie Roth","orcid":"0000-0002-5334-2077","position":2,"is_corresponding":false},{"id":1611198,"name":"Ernst Schmid","orcid":null,"position":3,"is_corresponding":false},{"id":51282,"name":"Karen Adelman","orcid":"0000-0001-5364-334X","position":4,"is_corresponding":false},{"id":1611200,"name":"Johannes C Walter","orcid":null,"position":5,"is_corresponding":false},{"id":58318,"name":"Lucas Farnung","orcid":"0000-0002-8200-2493","position":6,"is_corresponding":false},{"id":506512,"name":"Della Syau","orcid":"0000-0002-8192-2220","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structure and function of IWS1 in transcription elongation","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Transcription elongation by RNA polymerase II is a tightly regulated process that requires coordinated interactions between transcription elongation factors. IWS1 (Interacts with SPT6) has been implicated as a core elongation factor, but its molecular role remains unclear. We show that the intrinsically disordered C-terminal region of IWS1 contains short linear motifs (SLiMs) that multivalently engage the elongation machinery. Using cryo-electron microscopy, we map SLiMs in IWS1 that interact with Pol II subunits RPB1, RPB2, and RPB5, as well as elongation factors DSIF, SPT6, and ELOF1. Functional assays demonstrate that distinct IWS1 SLiMs specify IWS1 recruitment and IWS1-dependent transcription stimulation. IWS1 recruitment to the transcription elongation complex depends on association via the RPB1 jaw and binding of downstream DNA. Transcription elongation stimulation requires interactions with the RPB2 lobe and ELOF1. We identify other transcription elongation factors including ELOA and RECQL5 that bind the RPB1 jaw and demonstrate that IWS1 protects the activated transcription elongation complex from RECQL5 inhibition. We also reveal the binding of the histone reader and IWS1 interactor LEDGF to a transcribed downstream nucleosome. Our findings establish IWS1 as a modular scaffold that helps organize the transcription elongation complex, illustrating how disordered regions regulate transcription elongation.</jats:p>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42134803","pmcid":null,"openalex_id":"https://openalex.org/W4413834411","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"DP2-ES036404","title":null},{"funder_name":"National Institutes of Health","grant_id":"HL098316","title":null},{"funder_name":"National Institutes of Health","grant_id":"R01GM139960","title":null},{"funder_name":"National Science Foundation","grant_id":"DGE 2140743","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL098316","title":null},{"funder_name":"Damon Runyon Rachleff Innovator Award Program","grant_id":"","title":null},{"funder_name":"Boehringer Ingelheim Fonds","grant_id":"","title":null},{"funder_name":"Smith Family Awards Program","grant_id":"","title":null}],"total_grants":8,"fwci":3.8186,"citation_percentile":0.85839088,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1093/nar/gkag357","host_type":"journal"},{"url":"https://doi.org/10.1093/nar/gkag357","host_type":"publisher"},{"url":"https://academic.oup.com/nar/article-pdf/54/9/gkag357/68278485/gkag357.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1101/2025.08.28.672863","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40909601","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42134803","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12407956/","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13175633/","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/08/28/2025.08.28.672863.full.pdf","host_type":"repository"}],"fields_of_study":["RNA and protein synthesis mechanisms","RNA Research and Splicing","interferon and immune responses","Transcription Elongation, Genetic","Transcriptional Elongation Factors","RNA Polymerase II","Cryoelectron Microscopy","Protein Binding","Transcription Factors","Amino Acid Motifs"],"mesh_terms":["Transcription Elongation, Genetic","Transcriptional Elongation Factors","RNA Polymerase II","Cryoelectron Microscopy","Protein Binding","Transcription Factors","Amino Acid Motifs"],"keywords":["RNA polymerase II","Transcription (linguistics)","Elongation factor","Cell biology","Elongation","Transcription factor","Transcription factor II F","Biology","Transcription preinitiation complex","General transcription factor","Transcription factor II D","Molecular biology","Genetics","Promoter","RNA polymerase","RNA","Transcriptional regulation","Gene expression","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T23:46:16.182365Z","pmid":null,"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":[]}