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Article

Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania

1
Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA
2
Honors College, Texas Tech University, Lubbock, TX 79409, USA
3
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
4
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: Gabriela Santos-Gomes and Maria Pereira
Biomedicines 2021, 9(6), 696; https://doi.org/10.3390/biomedicines9060696
Received: 18 May 2021 / Revised: 9 June 2021 / Accepted: 15 June 2021 / Published: 19 June 2021
(This article belongs to the Special Issue Parasitic Infection and Immunity)
Leishmania parasites are trypanosomatid protozoans that cause leishmaniasis affecting millions of people worldwide. Sterols are important components of the plasma and organellar membranes. They also serve as precursors for the synthesis of signaling molecules. Unlike animals, Leishmania does not synthesize cholesterol but makes ergostane-based sterols instead. C-14-demethylase is a key enzyme involved in the biosynthesis of sterols and an important drug target. In Leishmania parasites, the inactivation of C-14-demethylase leads to multiple defects, including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C-14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis in Leishmania plays an unexpected role in global gene regulation. View Full-Text
Keywords: Leishmania; sterol; C-14-demethylase; stress tolerance; RNA degradation; polysome; endoplasmic reticulum; translation; regulation of gene expression Leishmania; sterol; C-14-demethylase; stress tolerance; RNA degradation; polysome; endoplasmic reticulum; translation; regulation of gene expression
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MDPI and ACS Style

Karamysheva, Z.N.; Moitra, S.; Perez, A.; Mukherjee, S.; Tikhonova, E.B.; Karamyshev, A.L.; Zhang, K. Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania. Biomedicines 2021, 9, 696. https://doi.org/10.3390/biomedicines9060696

AMA Style

Karamysheva ZN, Moitra S, Perez A, Mukherjee S, Tikhonova EB, Karamyshev AL, Zhang K. Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania. Biomedicines. 2021; 9(6):696. https://doi.org/10.3390/biomedicines9060696

Chicago/Turabian Style

Karamysheva, Zemfira N., Samrat Moitra, Andrea Perez, Sumit Mukherjee, Elena B. Tikhonova, Andrey L. Karamyshev, and Kai Zhang. 2021. "Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania" Biomedicines 9, no. 6: 696. https://doi.org/10.3390/biomedicines9060696

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