Fig. 3.

Other mechanisms of translation regulation. Despite a loss in the ternary complex after ISR, the synthesis of certain proteins, like CHOP and ATF4, is enhanced by leaky scanning (A) and delayed reinitiation (B) mechanism, respectively. The reduced availability of eIF2 in stressed conditions allows for the scanning ribosomes to bypass (i.e., leaky scanning) the uORF in the 5′ UTR and translate the mORF. This is the case for CHOP and GADD34. Some genes, like ATF4, contain multiple uORFs in which one of the uORFs overlaps with the mORF in an out-of-frame manner, thereby suppressing the expression of the main gene. During ISR, the delay in eIF2 recycling allows for the scanning ribosome to skip the start codon of uORF and instead translate the mORF.