eIF5A promotes translation elongation, polysome disassembly and stress granule assembly.
Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate in cells exposed to environmental stress. We have identified ornithine decarboxylase (ODC), an enzyme required for polyamine synthesis, and eIF5A, a polyamine (hypusine)-modified translation factor, as proteins required for arsenite-induced SG assembly. Knockdown of deoxyhypusine synthase (DHS) or treatment with a deoxyhypusine synthase inhibitor (GC7) prevents hypusine modification of eIF5A as well as arsenite-induced polysome disassembly and stress granule assembly. Time-course analysis reveals that this is due to a slowing of stress-induced ribosome run-off in cells lacking hypusine-eIF5A. Whereas eIF5A only marginally affects protein synthesis under normal conditions, it is required for the rapid onset of stress-induced translational repression. Our results reveal that hypusine-eIF5A-facilitated translation elongation promotes arsenite-induced polysome disassembly and stress granule assembly in cells subjected to adverse environmental conditions.
Li
Chi Ho
CH
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Ohn
Takbum
T
Ivanov
Pavel
P
Tisdale
Sarah
S
Anderson
Paul
P
D018053:Arsenites / Q000494:pharmacology; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011132:Polyribosomes / Q000378:metabolism*; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological; D000097574:Eukaryotic Translation Initiation Factor 5A
D018053:Arsenites; D008239:Lysine; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100028:hypusine; C015001:arsenite