GSE70211 | Datasets2Tools

General Information

Accession	GSE70211
Title	Rocaglamide A converts RNA helicase eIF4A into a sequence-specific translational repressor
Description	Rocaglamide A (RocA) typifies a novel class of protein synthesis inhibitors that selectively kill aneuploid tumor cells and repress translation of specific mRNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), the prototypical DEAD-box RNA helicase, and its mRNA selectivity is proposed to reflect highly structured 5 UTRs that are very dependent on eIF4A-mediated unwinding. Here, we show that secondary structure in 5 UTRs is only a minor determinant for RocA selectivity and RocA does not repress translation by reducing eIF4A activity. Rather, in vitro and in vivo, RocA clamps eIF4A onto a specific sequence motif even after ATP hydrolysis. This artificially clamped eIF4A blocks 43S scanning, leading to premature, upstream translation initiation and reducing gene expression on transcripts bearing the RocA-eIF4A target sequence. In elucidating the mechanism of this lead anti-cancer compound and explaining its mRNA selectivity, we provide the first example of a drug stabilizing sequence-specific RNA-protein interactions.
Landing Page	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70211
Repository	Gene Expression Omnibus