Translation initiation can be (a) cap-dependent and/or (b) IRES-dependent. Using the color code, only the primary factors mentioned in the text have been depicted for simplicity. Cellular mRNAs functionally pseudo-circularize as a result of the interaction between eIF4G and PABP. Regarding the FMDV genome, the 5′-3′ long-range communication among the 3′-UTR with the S fragment (a large stem-loop formed by the folding of the terminal structure at the 5′ end), in addition to 3′ UTR-IRES interaction, permits a comparable circumstance that is probably stabilized by binding factors for RNA. IRES-driven translational initiation requires a few eIFs and IRES-transacting factors (ITAFs), i.e., PCBP2, PTB, and Germin 5 which modulate IRES activity. 3C is crucial because it guarantees the internal initiation of translation by cleaving certain eIFs and ITAFs.