Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Yimin, Lin, Mi, Chen, Xueqiu, Zhao, XianFeng, Chen, Lulu, Zhao, Mingxiu, Yao, Chaoqun, Sheng, Kaiyin, Yang, Yi, Ma, Guangxu, Du, Aifang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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
_version_ 1784777477499912192
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
title_full The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
title_fullStr The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
title_full_unstemmed The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
title_short The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii
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
work_keys_str_mv AT yangyimin thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT linmi thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT chenxueqiu thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT zhaoxianfeng thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT chenlulu thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT zhaomingxiu thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT yaochaoqun thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT shengkaiyin thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT yangyi thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT maguangxu thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT duaifang thefirstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT yangyimin firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT linmi firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT chenxueqiu firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT zhaoxianfeng firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT chenlulu firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT zhaomingxiu firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT yaochaoqun firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT shengkaiyin firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT yangyi firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT maguangxu firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii
AT duaifang firstapicoplasttrnathiouridylaseplaysavitalroleinthegrowthoftoxoplasmagondii