Selective targeting of the DEAD-box RNA helicase eukaryotic initiation factor (eIF) 4A by natural products

Covering: up to 2019 Pharmacological targeting of eukaryotic mRNA translation initiation is a promising approach for cancer therapy, since several signaling pathways that are commonly deregulated during tumor progression converge on this process. The DEAD-box helicase, eukaryotic initiation factor (eIF) 4A, is essential for translation initiation and facilitates the loading of the 43S pre-initiation complex onto mRNAs. Hippuristanol, rocaglates, and pateamine A are natural products that each target eIF4A by interfering with the helicase's RNA-binding activity in distinct manners. They exert a selective change in gene expression that results in potent anti-tumorigenic activity in pre-clinical studies. This review will provide an update on the molecular mechanisms of action of these natural products. This highlight reviews natural products targeting of the eIF4A RNA helicase by interfering with RNA-binding or acting as interfacial inhibitors to increase RNA resident time.