Stress granules are dense aggregations in the cytosol composed of proteins & RNAs that appear when the cell is under stress The RNA molecules stored are stalled translation pre-initiation complexes: failed attempts to make protein from mRNA. Stress granules are 100–200 nm...
NEDDylation promotes stress granule assembly.
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Nature communications, ISSN: 2041-1723, Vol: 7, Page: 12125
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- Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy; Post-translational modifications; Stress granules; Stress signalling; Ubiquitin ligases; Cell Anatomy; Medicine and Health Sciences; Microbiology
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Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly.