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

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 activit...

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Main Authors: Sasi Kumar Jagadeesan, Mustafa Al-gafari, Jiashu Wang, Sarah Takallou, Danielle Allard, Maryam Hajikarimlou, Thomas David Daniel Kazmirchuk, Houman Moteshareie, Kamaledin B. Said, Reza Nokhbeh, Myron Smith, Bahram Samanfar, Ashkan Golshani
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/2/1785
Description
Summary: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 <i>PGM2</i>, 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 <i>DBP7</i>∆ and <i>YRF1-6</i>∆ exhibit increased LiCl sensitivity on galactose-containing media. Additionally, we demonstrate that <i>DBP7</i> and <i>YRF1-6</i> modulate the translational level of <i>PGM2</i> mRNA, and the observed alteration in translation seems to be associated with the 5′-untranslated region (UTR) of <i>PGM2</i> mRNA. Furthermore, we observe that <i>DBP7</i> and <i>YRF1-6</i> influence, to varying degrees, the translation of other mRNAs that carry different 5′-UTR secondary structures.
ISSN:1661-6596
1422-0067