title: Cytosolic accumulation of small nucleolar RNAs (snoRNAs) is dynamically regulated by NADPH oxidase.
abstract: 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.
authors: From the Diabetic Cardiovascular Disease Center and.
authors: Christopher L
authors: CL
authors: Holley
authors: From the Diabetic Cardiovascular Disease Center and.
authors: Melissa W
authors: MW
authors: Li
authors: From the Diabetic Cardiovascular Disease Center and.
authors: Benjamin S
authors: BS
authors: Scruggs
authors: Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missiouri 63110.
authors: Scot J
authors: SJ
authors: Matkovich
authors: From the Diabetic Cardiovascular Disease Center and.
authors: Daniel S
authors: DS
authors: Ory
authors: From the Diabetic Cardiovascular Disease Center and jschaff@wustl.edu.
authors: Jean E
authors: JE
authors: Schaffer
mesh_terms: D000818:Animals; D055162:Biocatalysis; D001692:Biological Transport / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012269:Ribosomal Proteins / Q000235:genetics; D013481:Superoxides / Q000378:metabolism
chemical_list: D020537:RNA, Small Nucleolar; D012269:Ribosomal Proteins; C489210:Rpl13a protein, rat; D013481:Superoxides; D004317:Doxorubicin; D019255:NADPH Oxidases
keywords: Doxorubicin; Intracellular Trafficking; Molecular Cell Biology; NADPH Oxidase; Reactive Oxygen Species (ROS); Small Nucleolar RNA (snoRNA); Subcellular Fractionation