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Series GSE150111 Query DataSets for GSE150111
Status Public on Dec 07, 2020
Title Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A [Bind-n-Seq]
Organism synthetic construct
Experiment type Other
Summary Small molecule compounds that sense the nucleic acid sequences, promise the attractive venue for drug development. Such an unusual effect has been observed in the natural product Rocaglamide A (RocA) from Aglaia plant, proving to exhibit anti-tumor effects by clamping eukaryotic initiation factor (eIF) 4A onto mRNA polypurine sequences. Although eIF4A has been speculated the unique target of RocA, the insensitization of eIF4A in human cells only partially rescued the translation repression from RocA, suggesting another alternative target of this compound. Here, we revealed that DDX3 is an alternative target of RocA. Developing a RocA derivative with an O-nitrobenzoxadiazole unit (RocA-O-NBD), which can covalently bind to proximate proteins and provide fluorescence to them, we identified DDX3 bound to RocA. As observed in eIF4A, RocA locked the DDX3 protein onto polypurine sequences of RNA in an ATP-independent manner. De novo assembled Aglaia plant transcriptome uncovered the natural amino acid substitutions in Aglaia DDX3 to protect itself from RocA toxicity. Because of the dominant negative effect of RocA, we also proved the protein abundance of eIF4A and DDX3 in cancer cells determines their sensitivity to RocA. Overall, this study discovered DDX3 as another target of RocA and suggests the probability to predict tumor toxicity of RocA by the target abundance.
Overall design Bind-n-Seq
Contributor(s) Chen M, Shichino Y, Iwasaki S
Citation(s) 33296667
Submission date May 08, 2020
Last update date Mar 08, 2021
Contact name Mingming Chen
Phone 07031428686
Organization name RIKEN
Department CPR
Lab RNA systems biochemistry lab
Street address Hirisawa 2-2
City Wakoshi
State/province Saitama
ZIP/Postal code 351-0106
Country Japan
Platforms (1)
GPL21616 Illumina HiSeq 4000 (synthetic construct)
Samples (7)
GSM4523759 DDX3_input_ATP
BioProject PRJNA631213
SRA SRP260667

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE150111_RAW.tar 30.0 Kb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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