A Two-Part Rocaglate Helps Multiple eIF4A Proteins Bind RNA Together
Updated
Abstract
BisRoc, a dimeric ligand, potently and durably suppresses translation and shows greater specificity across cancer cell lines compared to the monomeric RocA.
- BisRoc's effectiveness is influenced by the cellular environment, including mechanisms for uptake and transport.
- Different forms of the translation initiation factor, eIF4A1 and eIF4A2, respond differently to BisRoc-induced dimerization.
- BisRoc enhances the assembly of RNA-binding protein complexes that promote stress-granule formation more efficiently than RocA.
- The approach of ligand dimerization could potentially be applied to influence the assembly of other RNA-binding proteins.
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Funding
Competing interests
Competing interests K.M.S. receives stock and/or cash compensation from: BridGene Biosciences, Erasca, G Protein Therapeutics, Genentech/Roche, Kumquat Biosciences, Kura Oncology, Lyterian, Merck, Montara, Nextech, Pfizer, Revolution Medicines, Rezo, Tahoe Therapeutics, Totus, Type6 Therapeutics, Wellspring Biosciences (Araxes Pharma). Kin of K.L. hold stock in and are employed by Pharmaron. L.A.G has filed patents on CRISPR functional genomics. L.A.G consults for, has equity in and is a co-founder of nChroma Bio.
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