Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2

The circadian clock regulates gene expression for up to 50% of expressed genes in eukaryotes.

• The circadian clock influences the activation of mitogen-activated protein kinase (MAPK) pathways in Neurospora crassa.
• Osmotic stress leads to phosphorylation of a kinase (RCK-2) that is essential for the phosphorylation of eukaryotic elongation factor-2 (eEF-2), a critical regulator of protein synthesis.
• Phosphorylation levels of RCK-2 and eEF-2 exhibit rhythmic patterns in wild-type cells, but these rhythms are absent in cells lacking OS-2 or the core clock component FREQUENCY (FRQ).
• Translation activity decreases during the late subjective morning, aligning with peak phosphorylation of eEF-2.
• Circadian regulation of eEF-2 activity is required for rhythmic translation of specific mRNAs, such as glutathione S-transferase (GST-3), but does not affect the accumulation of the clock protein FRQ.

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