{"doi":"10.3389/fcimb.2021.799024","title":"Tra2beta-Dependent Regulation of RIO Kinase 3 Splicing During Rift Valley Fever Virus Infection Underscores the Links Between Alternative Splicing and Innate Antiviral Immunity","abstract":"Rift Valley fever virus (RVFV) is an emerging pathogen that has potential to cause severe disease in humans and domestic livestock. Propagation of RVFV strain MP-12 is negatively impacted by the actions of RIOK3, a protein involved in the cellular immune response to viral infection. During RVFV infection, RIOK3 mRNA is alternatively spliced to produce an isoform that correlates with the inhibition of interferon β signaling. Here, we identify splicing factor TRA2-β (also known as TRA2beta and hTRA2-β) as a key regulator governing the relative abundance of RIOK3 splicing isoforms. Using RT-PCR and minigenes, we determined that TRA2-β interaction with RIOK3 pre-mRNA was necessary for constitutive splicing of RIOK3 mRNA, and conversely, lack of TRA2-β engagement led to increased alternative splicing. Expression of TRA2-β was found to be necessary for RIOK3's antiviral effect against RVFV. Intriguingly, TRA2-β mRNA is also alternatively spliced during RVFV infection, leading to a decrease in cellular TRA2-β protein levels. These results suggest that splicing modulation serves as an immune evasion strategy by RVFV and/or is a cellular mechanism to prevent excessive immune response. Furthermore, the results suggest that TRA2-β can act as a key regulator of additional steps of the innate immune response to viral infection.","journal":"Frontiers in Cellular and Infection Microbiology","year":2022,"id":272326,"datarank":0.5449871830839907,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.17225118561579067,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.17225118561579067,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":8,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":774690,"name":"Thomas C. Bisom","orcid":"0000-0002-0238-1156","position":1,"is_corresponding":false},{"id":938863,"name":"Hunter L. Grimes","orcid":null,"position":2,"is_corresponding":false},{"id":787077,"name":"Miyuki Hayashi","orcid":"0000-0001-8098-3024","position":3,"is_corresponding":false},{"id":218861,"name":"Jean-Marc Lanchy","orcid":null,"position":4,"is_corresponding":false},{"id":774691,"name":"J. Stephen Lodmell","orcid":"0000-0002-8087-5362","position":5,"is_corresponding":false},{"id":774689,"name":"Luke Adam White","orcid":"0000-0003-4548-0661","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:27:43.806977Z","pmid":"35127560","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":[]}