Figure 1.
A. Simplified model of eIF4F-dependent initiation displaying cap recognition and subsequent destabilization of local secondary structure. eIF4H and eIF4B share a common binding site on eIF4A and these interactions are mutually exclusive.111 Not shown is mRNA circularization mediated through poly(A) tail:poly(A)-binding protein (PABP) and eIF4G. B. Schematic diagram illustrating targets of various small molecules and anti-sense oligonucleotides (ASO) that target eIF4E-cap interaction (4Ei-1), prevent synthesis of the eIF4E subunit (4E ASO), inhibit eIF4E:eIF4G interaction (4E1RCat, 4E2RCat, 4E3RCat (unpublished data), 4EGI-1), and interfere with eIF4A helicase activity (silvestrol, hippuristanol, pateamine A). (Note that although ribavirin has been claimed to inhibit eIF4E-cap interaction,112 this has been questioned.113,114).