A Two-Part Protein Helps Multiple eIF4A Molecules Bind RNA Together

BisRoc, a dimeric rocaglate ligand, exhibits greater specificity across a cancer cell line panel than the monomeric RocA.

• Ligand dimerization enhances avidity, potency, and selectivity.
• BisRoc potently and durably suppresses translation in cancer cells.
• Cellular context, such as IFITM-mediated uptake and ABC-type efflux transporters, influences BisRoc activity.
• The paralogs eIF4A1 and eIF4A2 show different sensitivities to BisRoc-induced dimerization.
• BisRoc-bridged eIF4A-RNA complexes promote stress-granule formation more efficiently than monomeric RocA.
• This ligand dimerization strategy could potentially modulate the assembly of other RNA-binding proteins.

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