New insights into the topology of the scanning ribosome during translation initiation: Lessons from viruses

Location of the translation initiation codon generally requires scanning of the 43S ribosomal preinitiation complex (43S PIC) from the 5 of the mRNA. Associated RNA helicases can facilitate movement of the 43S PIC by removing secondary structure present in the 5 UTR of mRNA, which is required for codon inspection. The canonical RNA-dependent helicase eIF4A is directly involved in this process, as part of the eIF4F complex (eIF4G + eIF4A + eIF4E) that associates first with mRNA and then recruits the 43S PIC to initiate scanning. The topology and operational mechanism of the scanning PIC are probably the least understood aspects of the initiation step. Recent findings from translation of alphavirus mRNA, together with new biochemical and structural data of the 43S PIC, suggest a role for the ES6S region of 40S as the gateway for mRNA entry during scanning. The presence of eIF4G-eIF4A complex in this region, interacting with the incoming mRNA, supports a model where eIF4A could work ahead of the scanning complex during translation initiation. Here we present additional data supporting this model.