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

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 syn...

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Autores principales: Karamysheva, Zemfira N., Moitra, Samrat, Perez, Andrea, Mukherjee, Sumit, Tikhonova, Elena B., Karamyshev, Andrey L., Zhang, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235615/
https://www.ncbi.nlm.nih.gov/pubmed/34205466
http://dx.doi.org/10.3390/biomedicines9060696
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author Karamysheva, Zemfira N.
Moitra, Samrat
Perez, Andrea
Mukherjee, Sumit
Tikhonova, Elena B.
Karamyshev, Andrey L.
Zhang, Kai
author_facet Karamysheva, Zemfira N.
Moitra, Samrat
Perez, Andrea
Mukherjee, Sumit
Tikhonova, Elena B.
Karamyshev, Andrey L.
Zhang, Kai
author_sort Karamysheva, Zemfira N.
collection PubMed
description 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.
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spelling pubmed-82356152021-06-27 Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania Karamysheva, Zemfira N. Moitra, Samrat Perez, Andrea Mukherjee, Sumit Tikhonova, Elena B. Karamyshev, Andrey L. Zhang, Kai Biomedicines Article 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. MDPI 2021-06-19 /pmc/articles/PMC8235615/ /pubmed/34205466 http://dx.doi.org/10.3390/biomedicines9060696 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Karamysheva, Zemfira N.
Moitra, Samrat
Perez, Andrea
Mukherjee, Sumit
Tikhonova, Elena B.
Karamyshev, Andrey L.
Zhang, Kai
Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania
title Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania
title_full Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania
title_fullStr Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania
title_full_unstemmed Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania
title_short Unexpected Role of Sterol Synthesis in RNA Stability and Translation in Leishmania
title_sort unexpected role of sterol synthesis in rna stability and translation in leishmania
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235615/
https://www.ncbi.nlm.nih.gov/pubmed/34205466
http://dx.doi.org/10.3390/biomedicines9060696
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