Cytosolic accumulation of small nucleolar RNAs (snoRNAs) is dynamically regulated by NADPH oxidase

J Biol Chem. 2015 May 1;290(18):11741-8. doi: 10.1074/jbc.M115.637413. Epub 2015 Mar 19.

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.

Keywords: Doxorubicin; Intracellular Trafficking; Molecular Cell Biology; NADPH Oxidase; Reactive Oxygen Species (ROS); Small Nucleolar RNA (snoRNA); Subcellular Fractionation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biocatalysis
  • Biological Transport / drug effects
  • Cytosol / drug effects
  • Cytosol / metabolism*
  • Doxorubicin / pharmacology
  • NADPH Oxidases / metabolism*
  • Oxidative Stress / drug effects
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism*
  • Rats
  • Ribosomal Proteins / genetics
  • Superoxides / metabolism

Substances

  • RNA, Small Nucleolar
  • Ribosomal Proteins
  • Rpl13a protein, rat
  • Superoxides
  • Doxorubicin
  • NADPH Oxidases

Associated data

  • GEO/GSE67050