2023-01-192023-01-192021Karamysheva 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/biomedicines9060696https://doi.org/10.3390/biomedicines9060696https://hdl.handle.net/2346/90473© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).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.engLeishmaniaSterolC-14-DemethylaseStress ToleranceRNA DegradationPolysomeEndoplasmic ReticulumTranslationRegulation of Gene ExpressionArticle