Lithium Chloride Sensitivity in Yeast and Regulation of Translation

For decades, lithium chloride (LiCl) has been used as a treatment option for those living with bipolar disorder (BD). As a result, many studies have been conducted to examine its mode of action, toxicity, and downstream cellular responses. We know that LiCl is able to affect cell signaling and signaling transduction pathways through protein kinase C and glycogen synthase kinase-3, which are considered to be important in regulating gene expression at the translational level. However, additional downstream effects require further investigation, especially in translation pathway. In yeast, LiCl treatment affects the expression, and thus the activity, ofPGM2, a phosphoglucomutase involved in sugar metabolism. Inhibition ofPGM2leads to the accumulation of intermediate metabolites of galactose metabolism causing cell toxicity. However, it is not fully understood how LiCl affects gene expression in this matter. In this study, we identified three genes,NAM7,PUS2, andRPL27B, which increase yeast LiCl sensitivity when deleted. We further demonstrate thatNAM7,PUS2, andRPL27Binfluence translation and exert their activity through the 5 '-Untranslated region (5 '-UTR) ofPGM2mRNA in yeast.