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

Feb 4, 2025Proceedings of the National Academy of Sciences of the United States of America

The body clock controls how two proteins interact with ribosomes to regulate daily patterns of starting protein production

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Abstract

Circadian rhythms in mRNA translation through activity require rhythms in levels.

  • GCN2 activity is influenced by uncharged tRNA levels, which activate the kinase to phosphorylate eIF2α during nutrient starvation.
  • The circadian clock regulates the interaction of CPC-3 and with ribosomes, essential for maintaining CPC-3 activity rhythms.
  • A temperature-sensitive mutant with high uncharged tRNA levels disrupts rhythmic interactions and abolishes CPC-3 activity rhythms.
  • Disrupting the interaction between GCN1 and uncharged tRNA affects the rhythmic activity of CPC-3 in the absence of GCN20.
  • These findings suggest a mechanism linking circadian rhythms to the regulation of mRNA translation and cellular energy levels.

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