Figure 2.

Relationship between translated segments within the same RNA. (A) A schematic of metabolite-dependent translation regulation via ribosome arrest at uORF, such as in AMD1 mRNA. In the presence of a high concentration of polyamines, ribosomes with MAGDIS peptide stall at the end of the translon. (B) A schematic of delayed reinitiation mechanism enabling translation of selected mRNAs during global translation suppression caused by eIF2 complex phosphorylation during integrated stress response. When eIF2 is phosphorylated (specifically, serine 51 of its alpha subunit, encoded by EIF2S1), the concentration of the tRNAi*eIF2*GTP ternary complex (shown in red) decreases, and it requires a longer time and distance for the scanning ribosome complex to acquire it. As a result, the long uORF is bypassed, and initiation occurs at CDS.