{"doi":"10.1101/2021.09.14.460315","title":"Inositol hexakisphosphate is a critical regulator of Integrator assembly and function","abstract":"Integrator has critical roles in noncoding RNA 3′-end processing as well as transcription attenuation of selected mRNAs. IntS11 is the endonuclease for RNA cleavage, as a part of the IntS4-IntS9-IntS11 complex (Integrator cleavage module, ICM). Our structure of the Drosophila ICM, determined by cryo-electron microscopy at 2.74 Å resolution, unexpectedly revealed the stable association of an inositol hexakisphosphate (IP 6 ) molecule. The binding site is located in a highly electropositive pocket at an interface among all three subunits of ICM, 55 Å away from the IntS11 active site and generally conserved in other ICMs. IP 6 binding is also confirmed in human ICM. Mutations of residues in this binding site or disruption of IP 6 biosynthesis significantly reduced Integrator assembly and activity in snRNA 3′-end processing. Our structural and functional studies reveal that Integrator is subject to intricate cellular control and IP 6 is a critical regulator of Integrator assembly and function in Drosophila , humans, and likely other organisms.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221690,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9642,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":779489,"name":"Madeline K. Jensen","orcid":"0000-0002-8855-597X","position":1,"is_corresponding":false},{"id":250359,"name":"Nathan D. Elrod","orcid":"0000-0003-1310-6026","position":2,"is_corresponding":false},{"id":250357,"name":"Kai-Lieh Huang","orcid":"0000-0001-5407-648X","position":3,"is_corresponding":false},{"id":250364,"name":"Eric J. Wagner","orcid":"0000-0003-0217-383X","position":4,"is_corresponding":false},{"id":86983,"name":"Liang Tong","orcid":"0000-0002-0563-6468","position":5,"is_corresponding":false},{"id":822179,"name":"Min-Han Lin","orcid":"0000-0002-8639-0542","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:59.302331Z","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":[]}