{"doi":"10.1101/2025.11.21.689838","title":"Early Host-Virus RNA Interactions Reveal SPEN-Driven m <sup>6</sup> A Regulation as a Major Determinant of Henipavirus Infection","abstract":"SUMMARY Early interactions between viral RNA and host-encoded RNA-binding proteins are pivotal in shaping the trajectory of RNA virus infection. Henipaviruses are emerging, highly lethal BSL-4 pathogens whose mechanisms of pathogenesis remain largely elusive. To illuminate the earliest moments of host-virus interplay, we employed Viral Cross-linking and Solid-phase Purification (VIR-CLASP) to capture host proteins bound to the incoming henipavirus genome within the first hour of infection. This approach establishes the first henipavirus RNA-host protein interactome, revealing 146 human proteins directly associated with the primary viral RNA. Among these, SPEN, RBM15, and RBM15B - canonical regulators of lncRNA Xist – emerged as key host factors that actively promote viral infection. Direct RNA sequencing further uncovered that SPEN depletion induces widespread hypomethylation, affecting ~98% of differentially modified m 6 A sites, ~87% of which localize to the L mRNA transcript encoding the viral RNA-dependent RNA polymerase. Collectively, these findings expose a critical layer of host dependency at the very onset of infection and reveal a previously unappreciated role for SPEN family proteins in facilitating henipavirus infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":582893,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.967,"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":1494832,"name":"Stephen Clarke","orcid":"0000-0003-0830-1388","position":1,"is_corresponding":false},{"id":1495210,"name":"A. Livingston","orcid":null,"position":2,"is_corresponding":false},{"id":373867,"name":"Jackson B. Trotman","orcid":"0000-0003-3133-2393","position":3,"is_corresponding":false},{"id":877878,"name":"Sander Haigh","orcid":null,"position":4,"is_corresponding":false},{"id":1454595,"name":"Morad C. Malek","orcid":"0000-0002-6796-1899","position":5,"is_corresponding":false},{"id":275050,"name":"J. Mauro Calabrese","orcid":"0000-0002-1213-2540","position":6,"is_corresponding":false},{"id":276958,"name":"Manuel Ascano","orcid":"0000-0002-9370-5493","position":7,"is_corresponding":false},{"id":1494831,"name":"Andrea Ascura","orcid":"0009-0009-2962-884X","position":0,"is_corresponding":true}],"reference_count":134,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":"41332646","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":[]}