RNA-mediated sequestration of the RNA helicase eIF4A by Pateamine A inhibits translation initiation
- PMID: 17185224
- DOI: 10.1016/j.chembiol.2006.10.005
RNA-mediated sequestration of the RNA helicase eIF4A by Pateamine A inhibits translation initiation
Abstract
Eukaryotic initiation factor 4A (eIF4A) is a member of the DEAD-box family of putative RNA helicases whose members are involved in many aspects of RNA metabolism. eIF4A is thought to facilitate binding of 43S preinitiation complexes to mRNAs by unwinding secondary structures present in the 5' untranslated region. Pateamine A, a small-molecule inhibitor of translation initiation, acts in an unusual manner by stimulating eIF4A activity. Herein, we report the elucidation of pateamine's mode of action. We demonstrate that Pateamine A is a chemical inducer of dimerization that forces an engagement between eIF4A and RNA and prevents eIF4A from participating in the ribosome-recruitment step of translation initiation.
Comment in
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Translational dysregulation by Pateamine A.Chem Biol. 2007 Jan;14(1):5-7. doi: 10.1016/j.chembiol.2007.01.003. Chem Biol. 2007. PMID: 17254945 Free PMC article.
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