Dihydrocapsaicin induces translational repression and stress granule through HRI-eIF2α phosphorylation axis

Koushitak De, Aravinth Kumar Jayabalan, Ramesh Mariappan, Vijay Sankar Ramasamy, Takbum Ohn

Research output: Contribution to journalArticlepeer-review

Abstract

Stress granules (SGs) are cytoplasmic biomolecular condensates that are formed against a variety of stress conditions when translation initiation is perturbed. SGs form through the weak protein-protein, protein-RNA, and RNA-RNA interactions, as well as through the intrinsically disordered domains and post-translation modifications within RNA binding proteins (RBPs). SGs are known to contribute to cell survivability by minimizing the stress-induced damage to the cells by delaying the activation of apoptosis. Here, we find that dihydrocapsaicin (DHC), an analogue of capsaicin, is a SG inducer that promotes polysome disassembly and reduces global protein translation via phosphorylation of eIF2α. DHC-mediated SG assembly is controlled by the phosphorylation of eIF2α at serine 51 position and is controlled by all four eIF2α stress kinases (i.e., HRI, PKR, PERK, and GCN2) with HRI showing maximal effect. We demonstrate that DHC is a bonafide compound that induces SG assembly, disassembles polysome, phosphorylates eIF2α in an HRI dependent manner, and thereby arrest global translation. Together, our results suggest that DHC is a novel SG inducer and an alternate to sodium arsenite to study SG dynamics.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume588
DOIs
StatePublished - Jan 15 2022

Keywords

  • Biomolecular condensates
  • Dihydrocapsaicin
  • Stress granule
  • Stress kinases
  • Translation

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry
  • Cell Biology

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