A model for DAZAP1-mediated translational activation. DAZAP1 stimulates initiation by participating in or stabilizing end-to-end complex formation, which functionally links the 5′ and 3′ ends of the mRNA, enhancing small ribosomal subunit recruitment (filled arrow). Our results show that DAZAP1 can mediate this effect independently of the initial cap-binding step (denoted by broken line). DAZAP1 does not utilize Xdazl (denoted by a cross), but other proteins may mediate contact between DAZAP1 and PABP (factor Y), stabilizing complexes formed between PABP and eIF4G. Alternatively, DAZAP1 may contact factors at the 5′ end providing additional end-to-end contacts that help stabilize the closed-loop conformation. Since CSFV and the HAV IRES differ in their requirement for eIF4G, eIF4A, eIF4B, eIF1, or eIF1A, one of these 5′-bound factors may be contacted directly or indirectly (via factor Y) by DAZAP1; other eIFs are omitted for clarity. Direct interactions with eIF4G do not occur (denoted by a cross). Multiple DAZAP1 molecules are shown to indicate that target mRNAs benefit from multiple binding sites. Solid and dotted arrows indicate known and potential interactions, respectively. eIFs are denoted by their numbers or, with eIF4 factors, their letters: AAAA, poly(A) tail; Y, hypothetical factor(s); 40S, small ribosomal subunit; solid circle, 5′ cap; and curved box, open reading frame.
