UVC-induced stress granules in mammalian cells

• Published in: PloS one Vol. 9; no. 11; p. e112742
• Main Authors: Moutaoufik, Mohamed Taha, El Fatimy, Rachid, Nassour, Hassan, Gareau, Cristina, Lang, Jérôme, Tanguay, Robert M, Mazroui, Rachid, Khandjian, Edouard W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19-11-2014; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Arsenite; Biology and Life Sciences; Biomarkers - metabolism; Blockage; Cell culture; Cell cycle; Cell fusion; Cell growth; Cell Proliferation - radiation effects; Cytoplasm; Cytoplasm - metabolism; Cytoplasm - radiation effects; Decay; Deoxyribonucleic acid; DNA; DNA - biosynthesis; DNA repair; Dose-Response Relationship, Radiation; G1 phase; Granular materials; Granule cells; Heat treatment; Immunofluorescence; Initiation factor eIF-2; Intellectual disabilities; Irradiation; Kinases; Kinetics; Mammalian cells; Mammals; Mice; mRNA; Neurosciences; NIH 3T3 Cells; Phosphorylation; Physiology; Proteins; Radiation; Radiation damage; Ribonucleic acid; RNA; RNA-binding protein; Stress; Stresses; Studies; Ultraviolet Rays; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112742

Stress granules (SGs) are well characterized cytoplasmic RNA bodies that form under various stress conditions. We have observed that exposure of mammalian cells in culture to low doses of UVC induces the formation of discrete cytoplasmic RNA granules that were detected by immunofluorescence staining using antibodies to RNA-binding proteins. UVC-induced cytoplasmic granules are not Processing Bodies (P-bodies) and are bone fide SGs as they contain TIA-1, TIA-1/R, Caprin1, FMRP, G3BP1, PABP1, well known markers, and mRNA. Concomitant with the accumulation of the granules in the cytoplasm, cells enter a quiescent state, as they are arrested in G1 phase of the cell cycle in order to repair DNA damages induced by UVC irradiation. This blockage persists as long as the granules are present. A tight correlation between their decay and re-entry into S-phase was observed. However the kinetics of their formation, their low number per cell, their absence of fusion into larger granules, their persistence over 48 hours and their slow decay, all differ from classical SGs induced by arsenite or heat treatment. The induction of these SGs does not correlate with major translation inhibition nor with phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). We propose that a restricted subset of mRNAs coding for proteins implicated in cell cycling are removed from the translational apparatus and are sequestered in a repressed form in SGs.