Cytosolic Accumulation of Small Nucleolar RNAs (snoRNAs) is Dynamically Regulated by NADPH Oxidase. Rattus norvegicus

Small nucleolar RNAs (snoRNAs) guide nucleotide modifications of cellular RNAs in the nucleus. We have previously shown 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. Overall design: Cytosolic RNA was isolated from H9c2 cells by digitonin permeabilization of the plasma membrane and differential centrifugation. Cells were treated as follows: control, DPI (Nox inhibitor), doxorubicin (dox), or DPI+dox. N=3 independent experiments were analyzed for each treatment (12 samples total).