TY - JOUR
T1 - Dihydrocapsaicin induces translational repression and stress granule through HRI-eIF2α phosphorylation axis
AU - De, Koushitak
AU - Jayabalan, Aravinth Kumar
AU - Mariappan, Ramesh
AU - Ramasamy, Vijay Sankar
AU - Ohn, Takbum
N1 - Funding Information:
This study was supported by research fund from Chosun University , 2019.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/1/15
Y1 - 2022/1/15
N2 - 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.
AB - 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.
KW - Biomolecular condensates
KW - Dihydrocapsaicin
KW - Stress granule
KW - Stress kinases
KW - Translation
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U2 - 10.1016/j.bbrc.2021.12.049
DO - 10.1016/j.bbrc.2021.12.049
M3 - Article
C2 - 34953209
AN - SCOPUS:85121693537
SN - 0006-291X
VL - 588
SP - 125
EP - 132
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -