{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jiang X"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["116384"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12908447"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(10)"],"pubmed_abstract":["Spliceosome inhibitors emerged as promising anticancer agents. Recent studies have demonstrated that spliceosome-targeted therapies (STTs) trigger antitumor immune responses by inducing the accumulation of right-handed double-stranded (ds)RNA (A-RNA), resulting in the activation of RIG-I-like receptors (RLRs) and type I interferon-driven antiviral responses. Here, we show that spliceosome inhibition by pharmacological or genetic neutralization of SF3B1 activity induces the accumulation of endogenous left-handed dsRNAs (Z-RNAs) derived from intron-retained RNAs. These Z-RNAs activate the Z-form nucleic acid-sensor ZBP1, which triggers cell death in mouse embryonic fibroblasts and small cell lung cancer (SCLC) cells. Spliceosome inhibition induced potent ZBP1-dependent cell death in cancer-a"],"journal":["Cell reports"],"pubmed_title":["Spliceosome inhibition induces Z-RNA and ZBP1-driven cell death in small cell lung cancer."],"pmcid":["PMC12908447"],"funding_grant_id":["R37 CA283552","T32 GM142606","U54 CA221704"],"pubmed_authors":["Liu X","Zhang T","Canadas I","Kim W","Jiang X","Ma X","Zhou Y","Balachandran S"],"additional_accession":[]},"is_claimable":false,"name":"Spliceosome inhibition induces Z-RNA and ZBP1-driven cell death in small cell lung cancer.","description":"Spliceosome inhibitors emerged as promising anticancer agents. Recent studies have demonstrated that spliceosome-targeted therapies (STTs) trigger antitumor immune responses by inducing the accumulation of right-handed double-stranded (ds)RNA (A-RNA), resulting in the activation of RIG-I-like receptors (RLRs) and type I interferon-driven antiviral responses. Here, we show that spliceosome inhibition by pharmacological or genetic neutralization of SF3B1 activity induces the accumulation of endogenous left-handed dsRNAs (Z-RNAs) derived from intron-retained RNAs. These Z-RNAs activate the Z-form nucleic acid-sensor ZBP1, which triggers cell death in mouse embryonic fibroblasts and small cell lung cancer (SCLC) cells. Spliceosome inhibition induced potent ZBP1-dependent cell death in cancer-a","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-07-16T05:09:03.392Z","creation":"2026-07-10T03:09:08.212Z"},"accession":"S-EPMC12908447","cross_references":{"pubmed":["41046514"],"doi":["10.1016/j.celrep.2025.116384"]}}