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The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
Toxoplasmosis caused by the protozoan Toxoplasma gondii is one of the most common parasitic diseases in humans and almost all warm-blooded animals. Lys, Glu, and Gln-specific tRNAs contain a super-modified 2-thiourea (s(2)U) derivatives at the position 34, which is essential for all living organisms...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420914/ https://www.ncbi.nlm.nih.gov/pubmed/36046743 http://dx.doi.org/10.3389/fcimb.2022.947039 |
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author | Yang, Yimin Lin, Mi Chen, Xueqiu Zhao, XianFeng Chen, Lulu Zhao, Mingxiu Yao, Chaoqun Sheng, Kaiyin Yang, Yi Ma, Guangxu Du, Aifang |
author_facet | Yang, Yimin Lin, Mi Chen, Xueqiu Zhao, XianFeng Chen, Lulu Zhao, Mingxiu Yao, Chaoqun Sheng, Kaiyin Yang, Yi Ma, Guangxu Du, Aifang |
author_sort | Yang, Yimin |
collection | PubMed |
description | Toxoplasmosis caused by the protozoan Toxoplasma gondii is one of the most common parasitic diseases in humans and almost all warm-blooded animals. Lys, Glu, and Gln-specific tRNAs contain a super-modified 2-thiourea (s(2)U) derivatives at the position 34, which is essential for all living organisms by maintaining the structural stability and aminoacylation of tRNA, and the precision and efficiency of codon recognition during protein translation. However, the enzyme(s) involved in this modification in T. gondii remains elusive. In this report, three putative tRNA-specific 2-thiolation enzymes were identified, of which two were involved in the s(2)U34 modification of tRNA(Lys), tRNA(Glu), and tRNA(Gln). One was named TgMnmA, an apicoplast-located tRNA-specific 2-thiolation enzyme in T. gondii. Knockout of TgMnmA showed that this enzyme is important for the lytic cycle of tachyzoites. Loss of TgMnmA also led to abnormities in apicoplast biogenesis and severely disturbed apicoplast genomic transcription. Notably, mice survived from the infection with 10 TgMnmA-KO RH tachyzoites. These findings provide new insights into s(2)U34 tRNA modification in Apicomplexa, and suggest TgMnmA, the first apicoplast tRNA thiouridylase identified in all apicomplexans, as a potential drug target. |
format | Online Article Text |
id | pubmed-9420914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94209142022-08-30 The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii Yang, Yimin Lin, Mi Chen, Xueqiu Zhao, XianFeng Chen, Lulu Zhao, Mingxiu Yao, Chaoqun Sheng, Kaiyin Yang, Yi Ma, Guangxu Du, Aifang Front Cell Infect Microbiol Cellular and Infection Microbiology Toxoplasmosis caused by the protozoan Toxoplasma gondii is one of the most common parasitic diseases in humans and almost all warm-blooded animals. Lys, Glu, and Gln-specific tRNAs contain a super-modified 2-thiourea (s(2)U) derivatives at the position 34, which is essential for all living organisms by maintaining the structural stability and aminoacylation of tRNA, and the precision and efficiency of codon recognition during protein translation. However, the enzyme(s) involved in this modification in T. gondii remains elusive. In this report, three putative tRNA-specific 2-thiolation enzymes were identified, of which two were involved in the s(2)U34 modification of tRNA(Lys), tRNA(Glu), and tRNA(Gln). One was named TgMnmA, an apicoplast-located tRNA-specific 2-thiolation enzyme in T. gondii. Knockout of TgMnmA showed that this enzyme is important for the lytic cycle of tachyzoites. Loss of TgMnmA also led to abnormities in apicoplast biogenesis and severely disturbed apicoplast genomic transcription. Notably, mice survived from the infection with 10 TgMnmA-KO RH tachyzoites. These findings provide new insights into s(2)U34 tRNA modification in Apicomplexa, and suggest TgMnmA, the first apicoplast tRNA thiouridylase identified in all apicomplexans, as a potential drug target. Frontiers Media S.A. 2022-08-15 /pmc/articles/PMC9420914/ /pubmed/36046743 http://dx.doi.org/10.3389/fcimb.2022.947039 Text en Copyright © 2022 Yang, Lin, Chen, Zhao, Chen, Zhao, Yao, Sheng, Yang, Ma and Du https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Yang, Yimin Lin, Mi Chen, Xueqiu Zhao, XianFeng Chen, Lulu Zhao, Mingxiu Yao, Chaoqun Sheng, Kaiyin Yang, Yi Ma, Guangxu Du, Aifang The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii |
title | The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
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title_full | The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
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title_fullStr | The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
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title_full_unstemmed | The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
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title_short | The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
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title_sort | first apicoplast trna thiouridylase plays a vital role in the growth of toxoplasma gondii |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420914/ https://www.ncbi.nlm.nih.gov/pubmed/36046743 http://dx.doi.org/10.3389/fcimb.2022.947039 |
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