Circadian clock control of interactions between eIF2α kinase CPC-3 and GCN1 with ribosomes regulates rhythmic translation initiation.

Misregulation of the activity of GCN2, the kinase that phosphorylates and inactivates translation initiation factor eIF2α, has been implicated in several health disorders, underscoring the need to determine the mechanisms controlling GCN2 activation. During nutrient starvation, increased uncharged tRNA levels trigger GCN1 and GCN20 proteins to mediate the binding of uncharged tRNA to GCN2 to activate the kinase to phosphorylate eIF2α. Under constant conditions, activation of the homolog of GCN2, CPC-3, is controlled by the circadian clock.