A yeast model for eukaryotic reinitiation following translation of a short uORF. (A,B) eIF3 association with the scanning 48S PIC is stabilized by supporting contacts with eIF1, eIF1A, eIF5, and the TC. (C) Upon subunit joining, eIF3 (and possibly also eIF4F) remains bound to the 80S ribosomes owing to its strategic position on the solvent-exposed side of the 40S ribosome and the contacts that it makes with 40S ribosomal components (e.g., eIF3a-NTD with RPS0A) and presumably also with mRNA. (D) During the first few rounds of elongation, weakly associated eIF3 gradually dissociates from the 80S as a function of length and complexity of the translated region. (E,F) After translation of a short uORF, a certain proportion of 80S ribosomes terminating at its stop codon still contains eIF3, the presence of which is required for resumption of scanning. (E,G) Binding of the eIF3a-NTD directly to the specific eIF3a-RS 5′ of uORF1 greatly stabilizes association of the post-termination 40S subunit with mRNA following dissociation of the 60S subunit in the first stage of the ribosome recycling reaction and thereby promotes efficient resumption of scanning and REI downstream. (F,H) Absence of the stimulatory eIF3a-RS, for example at uORF4, results in completion of ribosomal recycling by the majority of terminating 80S ribosomes.