For the majority of eukaryotic messenger RNAs (mRNAs), translation initiates from a methionine-encoding AUG start codon following the molecular processes of 'cap-binding' and 'scanning' by ribosomal pre-initiation complexes (PICs). In rare exceptions, such as translation by viral IRES-containing mRNAs, 'cap-binding' and/or 'scanning' are not required for initiation, although AUG is still typically used as the first codon. RAN translation is an exception to the canonical rules as it uses variable start site selection and initiates from a non-AUG codon, but may still depend on 'cap-binding' and 'scanning'.[3]