Ksp1-dependent phosphorylation of eIF4G modulates post-transcriptional regulation of specific mRNAs under glucose deprivation conditions.

Post-transcriptional regulation is an important mechanism for modulating gene expression and is performed by numerous mRNA-binding proteins. To understand the mechanisms underlying post-transcriptional regulation, we investigated the phosphorylation status of 32 mRNA-binding proteins under glucose deprivation conditions in Saccharomyces cerevisiae. We identified 17 glucose-sensitive phosphoproteins and signal pathways implicated in their phosphorylation. Notably, phosphorylation of the eukaryotic translation initiation factor 4G (eIF4G) was regulated by both the Snf1/AMPK pathway and the target of rapamycin complex 1 (TORC1) pathway. The serine/threonine protein kinase Ksp1 has previously been suggested to be a downstream effector of TORC1, but its detailed function has rarely been discussed. We identified that Snf1/AMPK and TORC1 signalings converge on Ksp1, which phosphorylates eIF4G under glucose deprivation conditions. Ksp1-dependent phosphorylation of eIF4G regulates the degradation of specific mRNAs (e.g. glycolytic mRNAs and ribosomal protein mRNAs) under glucose deprivation conditions likely through the recruitment of Dhh1. Taken together, our results suggest that Ksp1 functions as a novel modulator of post-transcriptional regulation in yeast.