eIF1-eIF4G1 inhibitors uncover alternative translation activation of stress-response genes via enhanced ribosome loading and 5'UTR translation [MARS-seq]

The Ribo-seq and TI-seq analysis following i14G1s (eI1-eIF4G1 inhibitors) treatments uncover opposing roles of eIF1-eIF4G1 and eIF4E-eIF4G1 in scanning-dependent and independent translation. Furthermore, i14G1s inhibition of eIF4G1-eIF1 resulted in translation activation of ER/UPR stress-response genes via enhanced ribosome loading, elevated 5'UTR translation at near cognate AUGs, and unexpected concomitant upregulation of coding-region translation. Overall design: Ribo-seq and TI-seq analysis was performed either in HEK293T cells treated with either DMSO (vehicle control), i14G1-10 or i14G1-12.