eif5a promotes translation elongation, polysome disassembly and stress granule assemblyeif5a促进翻译伸长,多核糖体颗粒组装拆卸和压力.pdfVIP

eIF5A Promotes Translation Elongation, Polysome Disassembly and Stress Granule Assembly Chi Ho Li., Takbum Ohn.¤, Pavel Ivanov, Sarah Tisdale, Paul Anderson* Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America Abstract 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. Citation: Li CH, Ohn T, Ivanov P, Tisdale S, Anderson P (2010) eIF5A Promotes Translation Elongation, Polysome Disassembly and Stress Granule Assembly. PLoS ONE 5(4): e9942. doi:10.1371/journal.pone.0009942 Editor: Matt Kaeberlein, University of Washington, United States of America Received January 21, 2010; Accepted March 9, 2010; Published April 1, 2010 Copyright: 2010 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which