Datasets

Title	Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A
Organism
Number of Samples	16
Release Date	2020/04/14 00:00
Sequencing Types
Protocol Details

Title
Authors	Chen M,Asanuma M,Takahashi M,Shichino Y,Mito M,Fujiwara K,Saito H,Floor SN,Ingolia NT,Sodeoka M,Dodo K,Ito T,Iwasaki S
Journal	Cell chemical biology
Publication Date	2021 Apr 15
Abstract	The translation inhibitor rocaglamide A (RocA) has shown promising antitumor activity because it uniquely clamps eukaryotic initiation factor (eIF) 4A onto polypurine RNA for selective translational repression. As eIF4A has been speculated to be a unique target of RocA, alternative targets have not been investigated. Here, we reveal that DDX3 is another molecular target of RocA. Proximity-specific fluorescence labeling of an O-nitrobenzoxadiazole-conjugated derivative revealed that RocA binds to DDX3. RocA clamps the DDX3 protein onto polypurine RNA in an ATP-independent manner. Analysis of a de novo-assembled transcriptome from the plant Aglaia, a natural source of RocA, uncovered the amino acid critical for RocA binding. Moreover, ribosome profiling showed that because of the dominant-negative effect of RocA, high expression of eIF4A and DDX3 strengthens translational repression in cancer cells. This study indicates that sequence-selective clamping of DDX3 and eIF4A, and subsequent dominant-negative translational repression by RocA determine its tumor toxicity. Copyright © 2020 Elsevier Ltd. All rights reserved.
PMC	PMC8052261
PMID	33296667
DOI

Chen et al. 2020 (PRJNA625261)