Different modes of translation initiation. The eIF2 ternary complex, eIF1, eIF1A, eIF5, and eIF4B are not shown for simplicity. (A) Canonical cap-dependent translation. The small ribosomal subunit is recruited to the very 5′ end of mRNA by the eIF4E–eIF4G1–eIF3–40S interaction and then inspects the 5′ UTR of mRNA in the 3′ direction to locate the start codon (the scanning process). (B) IRES-mediated initiation. The small ribosomal subunit is recruited near the start codon of mRNA by the interaction of some translation initiation factors with specific secondary and tertiary structures. In the depicted case, the J-K domain of EMCV IRES attracts eIF4G1, forming a landing platform for the 40S ribosome. (C) CITE-mediated initiation. A tertiary structure or an RNA modification attracts the initiation factor (like the depicted N6-methyladenosine [m6A] attracts eIF3), then the 40S ribosomal complex is recruited and scanning starts from the very 5′ end of mRNA.
