Cap-dependent translation initiation begins by assembly of a pre-initiation ribosomal complex that scans the 5' Untranslated Region in order to localise the start codon. During this process, RNA secondary structures are melted by RNA helicases. Guenther et al reported that the yeast helicase Ded1, an orthologue of the mammalian DDX3 helicase, is responsible for this activity. When Ded1 is non-functional, RNA structures in the 5'UTR promote translation initiation on Alternative Translation Initiation Sites (ATIS) lead to uORF translation and consequently down-regulation of the main ORF. This mechanism is driven by the sole presence of RNA secondary structures located downstream of ATIS. Translation initiation mediated by RNA structures is found in other messenger RNAs. We propose to name this novel mechanism STructure-Assisted-RNA-Translation or START.
Keywords: Ded1/DDX3; RNA helicase; Translation initiation; messenger RNA; ribosome; scanning.