Cytosolic Accumulation of Small Nucleolar RNAs (snoRNAs) Is Dynamically Regulated by NADPH Oxidase

Small nucleolar RNAs (snoRNAs) guide nucleotide modifications of cellular RNAs in the nucleus. We previously showed that box C/D snoRNAs from the Rpl13a locus are unexpected mediators of physiologic oxidative stress, independent of their predicted ribosomal RNA modifications. Here we demonstrate that oxidative stress induced by doxorubicin causes rapid cytoplasmic accumulation of the Rpl13a snoRNAs through a mechanism that requires superoxide and a nuclear splice variant of NADPH oxidase. RNA-sequencing analysis reveals that box C/D snoRNAs as a class are present in the cytoplasm, where their levels are dynamically regulated by NADPH oxidase. These findings suggest that snoRNAs may orchestrate the response to environmental stress through molecular interactions outside of the nucleus. Background: Small nucleolar RNAs (snoRNAs) are thought to be exclusively nuclear. Results: Doxorubicin stress results in significant accumulation of cytosolic snoRNAs via a pathway involving Nox4D and superoxide. Conclusion: snoRNAs are present in the cytoplasm, and their cytosolic abundance is dynamically regulated. Significance: Previously unexplained snoRNA biology may be the result of snoRNA interactions with cytoplasmic targets.