DBP7 and YRF1-6 Are Involved in Cell Sensitivity to LiCl by Regulating the Translation of PGM2 mRNA

Abstract

Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal transduction pathways in mammalian cells, are shown to be regulated by LiCl. LiCl can negatively control the expression and activity of PGM2, a phosphoglucomutase that influences sugar metabolism in yeast. In the presence of galactose, when yeast cells are challenged by LiCl, the phosphoglucomutase activity of PGM2p is decreased, causing an increase in the concentration of toxic galactose metabolism intermediates that result in cell sensitivity. Here, we report that the null yeast mutant strains DBP7∆ and YRF1-6∆ exhibit increased LiCl sensitivity on galactose-containing media. Additionally, we demonstrate that DBP7 and YRF1-6 modulate the translational level of PGM2 mRNA, and the observed alteration in translation seems to be associated with the 5′-untranslated region (UTR) of PGM2 mRNA. Furthermore, we observe that DBP7 and YRF1-6 influence, to varying degrees, the translation of other mRNAs that carry different 5′-UTR secondary structures.

Hydrogen peroxide sensitivity connects the activity of COX5A and NPR3 to the regulation of YAP1 expression

“…The regulation of gene expression in response to stress has been an area of intense research 38,40–42 . Different types of stress, including oxidative stress, impose various challenges on the cell's viability.…”

“…The regulation of gene expression in response to stress has been an area of intense research. 38,[40][41][42] Different types of stress, including oxidative stress, impose various challenges on the cell's viability. As a consequence, cells respond by regulating the activity of certain pathways to promote cell survival.…”

Cymoxanil disrupts RNA synthesis through inhibiting the activity of dihydrofolate reductase

“…Specifically, single-gene deletion libraries are challenged by the compound of interest with the resulting biological responses providing indirect evidence of genetic targets (Fig. 1a) [23][24][25] . This approach has been used to elucidate the molecular activity of natural bioactive compounds 26,27 , pharmaceuticals 28 , nanoparticles 29 and herbal extracts 30 .…”

Investigating the Contribution of YPR089W, a Gene of Unknown Function, to Translation Initiation in Saccharomyces Cerevisiae

“…Lithium chloride (LiCl) is a well-established and widely used therapeutic agent with mental health benefits, particularly in the treatment of bipolar disorder (BD), and has been utilized for several decades 57,115 . Lithium has been found to have anti-mania, anti-depression, and antisuicide effects, and has been shown to help with treatment-resistant depression [115][116][117] .…”

“…Galactose is metabolized through the Leloir pathway, where it is first converted to galactose-1-phosphate by galactokinase, then to glucose-1-phosphate by galactose 1-phosphate uridyltransferase, and finally to glucose-6phosphate by a phosphoglucomutase (Pgm2) which can then enter into glycolysis 127 . However, LiCl inhibits this process by affecting the production of Pgm2, resulting in cell toxicity due to buildup of toxic intermediate metabolites that cannot proceed into glycolysis 57,128 . Notably, the PGM2 mRNA transcript has a structured region in its 5' UTR 125 .…”