Cap-dependent translation initiation in eukaryotes. Recruitment of the 43S preinitiation complex to the mRNA, mediated by factors of the eIF4 family and poly(A) binding protein (PABP), results in the formation of a 48S complex at the AUG initiator codon. Alternatively to the scenario shown here, eIF4E may remain bound to the cap during scanning (resulting in a looping-out of the 5′ UTR; Jackson 2000); in general, it remains to be established at which point after initial cap-binding the eIF4 factors dissociate from the mRNA and from PABP. Translation may also be initiated in cap-independent fashion, for instance by binding of the 43S complex to an internal ribosome entry site (IRES), which is typically located directly upstream of the AUG start codon (not shown; see Hellen & Sarnow 2001). Some factors (e.g., eIF5) have been omitted for clarity.