A novel class of mRNA-containing cytoplasmic granules are produced in response to UV-irradiation

Mol Biol Cell. 2008 Nov;19(11):4980-92. doi: 10.1091/mbc.e08-02-0193. Epub 2008 Sep 3.

Abstract

Nucleic acids are substrates for different types of damage, but little is known about the fate of damaged RNAs. We addressed the existence of an RNA-damage response in yeast. The decay kinetics of GAL1p-driven mRNAs revealed a dose-dependent mRNA stabilization upon UV-irradiation that was not observed after heat or saline shocks, or during nitrogen starvation. UV-induced mRNA stabilization did not depend on DNA repair, damage checkpoint or mRNA degradation machineries. Notably, fluorescent in situ hybridization revealed that after UV-irradiation, polyadenylated mRNA accumulated in cytoplasmic foci that increased in size with time. In situ colocalization showed that these foci are not processing-bodies, eIF4E-, eIF4G-, and Pab1-containing bodies, stress granules, autophagy vesicles, or part of the secretory or endocytic pathways. These results point to the existence of a specific eukaryotic RNA-damage response, which leads to new polyadenylated mRNA-containing granules (UV-induced mRNA granules; UVGs). We propose that potentially damaged mRNAs, which may be deleterious to the cell, are temporarily stored in UVG granules to safeguard cell viability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / drug effects
  • Autophagy / radiation effects
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / radiation effects*
  • Dose-Response Relationship, Radiation
  • Endocytosis / drug effects
  • Endocytosis / radiation effects
  • Galactokinase / genetics
  • Galactokinase / metabolism
  • Gene Expression Regulation, Fungal / drug effects
  • Gene Expression Regulation, Fungal / radiation effects
  • Heat-Shock Response / drug effects
  • Heat-Shock Response / radiation effects
  • Nitrogen / deficiency
  • Poly A / metabolism
  • Polyribosomes / drug effects
  • Polyribosomes / metabolism
  • Polyribosomes / radiation effects
  • RNA Stability / drug effects
  • RNA Stability / radiation effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / radiation effects*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sodium Chloride / pharmacology
  • Ultraviolet Rays*

Substances

  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Poly A
  • Sodium Chloride
  • GAL1 protein, S cerevisiae
  • Galactokinase
  • Nitrogen