Fig. 6: PERK-dependent RNA structural alterations control the translation of the human p47 isoform during ER stress.

Stress to the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) and PERK. PERK modulates the human p53 mRNA structure to facilitate alternative translation initiation from the 2nd AUG and the expression of the p47 isoform, independently of eIF2α. PERK-induced RNA structures downstream of the 2nd AUG promote the formation of a ribosome entry site upstream of the 2nd AUG. The murine p53 mRNA does not respond to PERK-mediated structural changes and the p44 isoform is not expressed. It is unknown which RNA chaperone(s) are responsible for PERK-induced RNA structural changes.