Figure 6.

Model of the HCV 3′UTR function in IRES-dependent translation. The two UTRs of HCV are brought to proximity by either long-range RNA–RNA kissing interactions or protein factors (16,17,40,45,46). At the termination stage of translation, when the stop codon is recognized by the A site, the variable region is presented to the 3′UTR binding region on the 40S subunit, promoting the 3′UTR-40S interaction. This interaction retains the 40S subunit after ribosome recycling and transfers it to the IRES in a favorable conformation for effective interactions, which can lead to efficient initiation for subsequence rounds of translation. Without the 3′UTR, for each round of translation, the IRES needs to recruit translation factors from the environment and sample through a variety of binding conformations with the 40S subunit, leading to inefficient initiation of translation.