NEDDylation promotes stress granule assembly

Aravinth Kumar Jayabalan, Anthony Sanchez, Ra Young Park, Sang Pil Yoon, Gum-Yong Kang, Je-Hyun Baek, Paul Anderson, Younghoon Kee and Takbum Ohn ()
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Aravinth Kumar Jayabalan: College of Medicine, Chosun University
Anthony Sanchez: Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida
Ra Young Park: College of Medicine, Chosun University
Sang Pil Yoon: School of Medicine, Jeju National University
Gum-Yong Kang: Diatech Korea Co, Ltd
Je-Hyun Baek: Diatech Korea Co, Ltd
Paul Anderson: Immunology and Allergy, Brigham and Women’s Hospital
Younghoon Kee: Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida
Takbum Ohn: College of Medicine, Chosun University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms12125

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