{"doi":"10.1016/j.celrep.2024.113998","title":"Initiation of a ZAKα-dependent ribotoxic stress response by the innate immunity endoribonuclease RNase L","abstract":"RNase L is an endoribonuclease of higher vertebrates that functions in antiviral innate immunity. Interferons induce oligoadenylate synthetase enzymes that sense double-stranded RNA of viral origin leading to the synthesis of 2',5'-oligoadenylate (2-5A) activators of RNase L. However, it is unknown precisely how RNase L remodels the host cell transcriptome. To isolate effects of RNase L from other effects of double-stranded RNA or virus, 2-5A is directly introduced into cells. Here, we report that RNase L activation by 2-5A causes a ribotoxic stress response involving the MAP kinase kinase kinase (MAP3K) ZAKα, MAP2Ks, and the stress-activated protein kinases JNK and p38α. RNase L activation profoundly alters the transcriptome by widespread depletion of mRNAs associated with different cellular functions but also by JNK/p38α-stimulated induction of inflammatory genes. These results show that the 2-5A/RNase L system triggers a protein kinase cascade leading to proinflammatory signaling and apoptosis.","journal":"Cell Reports","year":2024,"id":423256,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":252470,"name":"Goda Snieckute","orcid":"0000-0003-0738-0926","position":1,"is_corresponding":false},{"id":1218345,"name":"José Francisco Martı́nez","orcid":"0000-0002-3457-2088","position":2,"is_corresponding":false},{"id":1218346,"name":"Frederic Schrøder Arendrup","orcid":"0000-0001-6488-4616","position":3,"is_corresponding":false},{"id":737515,"name":"Abhishek Asthana","orcid":"0000-0002-5429-6199","position":4,"is_corresponding":false},{"id":493818,"name":"Christina Gaughan","orcid":"0000-0002-0869-9026","position":5,"is_corresponding":false},{"id":252478,"name":"Anders H. Lund","orcid":"0000-0002-7407-3398","position":6,"is_corresponding":false},{"id":252480,"name":"Simon Bekker‐Jensen","orcid":"0000-0002-7308-4597","position":7,"is_corresponding":false},{"id":301338,"name":"Robert H. Silverman","orcid":"0000-0003-2432-992X","position":8,"is_corresponding":false},{"id":1026344,"name":"Jiajia Xi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:57:56.814994Z","pmid":"38551960","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":[]}