Fig. 1: Canonical and non-canonical translation mechanisms.

A The conventional translation process commences with the formation of an mRNA closed-loop structure, facilitated by multiple interactions involving eIF4E with the mRNA cap and PABP with the poly(A)-tail. Subsequently, eIF4G binds to both eIF4E and eIF4A, forming the eIF4F complex. The eIF4F complex also interacts with PABP via eIF4G. This complex formation assists in recruiting the 43S PIC, comprising the 40S ribosomal subunit, eIF1, eIF1A, eIF3, eIF5, and the eIF2-GTP-Met-tRNAi ternary complex, to the mRNA cap. The 43S PIC then begins scanning from the 5′ to the 3′ direction in an ATP-dependent manner until it recognizes the AUG start codon. GTP hydrolysis then leads to the release of eIFs, allowing the large 60S ribosomal subunit to join and form the 80S ribosome. Translation continues until a stop codon is encountered, at which point the 80S complex is released, and the components are recycled for subsequent translation events. B Non-canonical translation mechanisms can occur independently of a cap or poly(A)-tail, and may utilize non-AUG start codons.