40S scanning unveiled by smFRET

Abstract

The longstanding scanning model of eukaryotic translation initiation states that the small (40S) ribosomal subunit is recruited to the 5′ end of the messenger RNA (mRNA) and then moves towards the 3′ end to locate the first start codon within a favorable sequence context, followed by recruitment of the large 60S subunit to begin protein synthesis. This process is orchestrated by numerous eukaryotic translation initiation factors (eIFs). Despite extensive biochemical, structural, and genetics analyses, scanning by 40S subunits has not been observed directly, hindering our mechanistic understanding of initiation.