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Lithium chloride sensitivity connects the activity of PEX11 and RIM20 to the translation of PGM2 and other mRNAs with structured 5’-UTRs

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Abstract

Lithium chloride (LiCl) is a widely used and extensively researched drug for the treatment of bipolar disorder (BD). As a result, LiCl has been the subject of research studying its toxicity, mode of action, and downstream cellular responses. LiCl has been shown to influence cell signaling and signaling transduction pathways through protein kinase C and glycogen synthase kinase-3 in mammalian cells. LiCl's significant downstream effects on the translational pathway necessitate further investigation. In yeast, LiCl is found to lower the activity and alter the expression of PGM2, a gene encoding a sugar-metabolism enzyme phosphoglucomutase. When phosphoglucomutase activity is reduced in the presence of galactose, intermediates of galactose metabolism aggregate, causing cell sensitivity to LiCl. In this study, we identified that deleting the genes PEX11 and RIM20 increases yeast LiCl sensitivity. We further show that PEX11 and RIM20 regulate the expression of PGM2 mRNA at the translation level. The observed alteration of translation seems to target the structured 5′-untranslated region (5′-UTR) of the PGM2 mRNA.

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Authors and Affiliations

  1. Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, ON, K1S 5B6, Canada

    Sasi Kumar Jagadeesan, Mustafa Al-gafari, Maryam Hajikarimlou, Sarah Takallou, Myron Smith & Ashkan Golshani

  2. Biotechnology Laboratory, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada

    Houman Moteshareie & Azam Tayabali

  3. Agriculture and Agri-Food Canada, Ottawa Research and Development Centre (ORDC), Ottawa, ON, Canada

    Bahram Samanfar

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  1. Sasi Kumar Jagadeesan
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Contributions

Sasi Kumar Jagadeesan (SJ) is responsible for conceptualization, data curation, formal analysis, investigation, methodology, validation, visualization, and paper writing. Ashkan Golshani (AG) is responsible for conceptualization, data curation, funding acquisition, project management, supervision, validation paper- review & editing. Mustafa Al-gafari (MA) supported with genetic interaction analysis and writing. Azam Tayabli (AT) is responsible for data interpretation, supervision, and writing. Maryam Hajikarimlou (MH) contributed to methodology, and data validation. Sarah Takallou (ST) assisted with experimental analysis, which included β-galactosidase analysis and quantitative polymerase chain reaction (qPCR) analysis. Houman Moteshareie (HM) contributed to western blot analysis and data interpretation. Myron Smith (MS) is responsible for investigation, supervision, and writing. Bahram Samanfar (BS) is responsible for supervision, data curation, methodology, and writing. This work is dedicated to the loving memory of Mrs. Minoo Golshani who dedicated her life to helping others.

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Correspondence to Ashkan Golshani.

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Jagadeesan, S.K., Al-gafari, M., Hajikarimlou, M. et al. Lithium chloride sensitivity connects the activity of PEX11 and RIM20 to the translation of PGM2 and other mRNAs with structured 5’-UTRs. Mol Cell Biochem 477, 2643–2656 (2022). https://doi.org/10.1007/s11010-022-04466-5

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