A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress

Cellular adaptation during metabolic stress Cells respond to environmental stress by down-regulating general protein synthesis and inducing selective expression of proteins required for survival. However, the mechanisms controlling this selective messenger RNA (mRNA) translation response remain poorly understood. Lamper et al. report that the noncanonical 5′ cap-binding protein subunit eIF3d is activated upon metabolic stress in mammalian cells to reprogram cellular mRNA translation. eIF3d is activated by a switch in phosphorylation status at sites near the cap-binding pocket and enables cells to express the proteins required for the regulation of metabolism and survival during stresses, including glucose starvation. This work reveals how eIF3d-dependent, noncanonical cap-dependent translation controls the cellular adaptation to stress. Science , this issue p. 853