Novel Role of SnoRNAs in Proteasome Inhibitor Induced Apoptosis

Small nucleolar RNAs (snoRNA) are 60-300 nucleotide long RNAs that guide modification of rRNAs during ribosome biogenesis. Many of them have non-canonical functions, such as regulation of splicing, pseudouridylation, and 2’-O-methylation of specific mRNAs. We have made a serendipitous discovery that treatment of cells with proteasome inhibitors (PIs) induces expression of several snoRNAs, including SNORD3 and SNORA71 families. Two other agents that induce production of misfolded proteins, tunicamycin and thapsigargin, also induced these snoRNAs, but DNA-damaging agent doxorubicin did not. Knocking SNORA71D down reduced PI-induced apoptosis. These findings indicate a novel and unexpected role of snoRNAs in proteasome inhibitor induced apoptosis. Citation Format: Alexei F. Kisselev, Olasubomi A. Akintola, Chandler R. Earley, Addison M. Wilson, Amit Kumar Mitra. A novel role of snoRNAs in proteasome inhibitor induced apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5898.