Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine

Abstract The phylum Apicomplexa comprises eukaryotic parasites that cause fatal diseases affecting millions of people and animals worldwide. Their mitochondrial genomes have been significantly reduced, leaving only three protein-coding genes and highly fragmented mitoribosomal rRNAs, raising challen...

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Main Authors: Chaoyue Wang, Sari Kassem, Rafael Eduardo Oliveira Rocha, Pei Sun, Tan-Trung Nguyen, Joachim Kloehn, Xianyong Liu, Lorenzo Brusini, Alessandro Bonavoglia, Sramona Barua, Fanny Boissier, Mayara Lucia Del Cistia, Hongjuan Peng, Xinming Tang, Fujie Xie, Zixuan Wang, Oscar Vadas, Xun Suo, Yaser Hashem, Dominique Soldati-Favre, Yonggen Jia
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55033-z
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author Chaoyue Wang
Sari Kassem
Rafael Eduardo Oliveira Rocha
Pei Sun
Tan-Trung Nguyen
Joachim Kloehn
Xianyong Liu
Lorenzo Brusini
Alessandro Bonavoglia
Sramona Barua
Fanny Boissier
Mayara Lucia Del Cistia
Hongjuan Peng
Xinming Tang
Fujie Xie
Zixuan Wang
Oscar Vadas
Xun Suo
Yaser Hashem
Dominique Soldati-Favre
Yonggen Jia
author_facet Chaoyue Wang
Sari Kassem
Rafael Eduardo Oliveira Rocha
Pei Sun
Tan-Trung Nguyen
Joachim Kloehn
Xianyong Liu
Lorenzo Brusini
Alessandro Bonavoglia
Sramona Barua
Fanny Boissier
Mayara Lucia Del Cistia
Hongjuan Peng
Xinming Tang
Fujie Xie
Zixuan Wang
Oscar Vadas
Xun Suo
Yaser Hashem
Dominique Soldati-Favre
Yonggen Jia
author_sort Chaoyue Wang
collection DOAJ
description Abstract The phylum Apicomplexa comprises eukaryotic parasites that cause fatal diseases affecting millions of people and animals worldwide. Their mitochondrial genomes have been significantly reduced, leaving only three protein-coding genes and highly fragmented mitoribosomal rRNAs, raising challenging questions about mitoribosome composition, assembly and structure. Our study reveals how Toxoplasma gondii assembles over 40 mt-rRNA fragments using exclusively nuclear-encoded mitoribosomal proteins and three lineage-specific families of RNA-binding proteins. Among these are four proteins from the Apetala2/Ethylene Response Factor (AP2/ERF) family, originally known as transcription factors in plants and Apicomplexa, now repurposed as essential mitoribosome components. Cryo-EM analysis of the mitoribosome structure demonstrates how these AP2 proteins function as RNA binders to maintain mitoribosome integrity. The mitoribosome is also decorated with members of lineage-specific RNA-binding proteins belonging to RAP (RNA-binding domain abundant in Apicomplexa) proteins and HPR (heptatricopeptide repeat) families, highlighting the unique adaptations of these parasites. Solving the molecular puzzle of apicomplexan mitoribosome could inform the development of therapeutic strategies targeting organellar translation.
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spelling doaj-art-c19e99e4416543799d958e64eb7fe31a2024-12-22T12:36:17ZengNature PortfolioNature Communications2041-17232024-12-0115111810.1038/s41467-024-55033-zApicomplexan mitoribosome from highly fragmented rRNAs to a functional machineChaoyue Wang0Sari Kassem1Rafael Eduardo Oliveira Rocha2Pei Sun3Tan-Trung Nguyen4Joachim Kloehn5Xianyong Liu6Lorenzo Brusini7Alessandro Bonavoglia8Sramona Barua9Fanny Boissier10Mayara Lucia Del Cistia11Hongjuan Peng12Xinming Tang13Fujie Xie14Zixuan Wang15Oscar Vadas16Xun Suo17Yaser Hashem18Dominique Soldati-Favre19Yonggen Jia20National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural UniversityDepartment of Microbiology and Molecular Medicine, University of GenevaINSERM U1212 Acides nucléiques: Régulations Naturelle et Artificielle (ARNA), Institut Européen de Chimie et Biologie, Université de BordeauxGuangdong Key Laboratory of Animal Conservation and Resource Utilization, Institute of Zoology, Guangdong Academy of ScienceINSERM U1212 Acides nucléiques: Régulations Naturelle et Artificielle (ARNA), Institut Européen de Chimie et Biologie, Université de BordeauxDepartment of Microbiology and Molecular Medicine, University of GenevaNational Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural UniversityDepartment of Microbiology and Molecular Medicine, University of GenevaDepartment of Microbiology and Molecular Medicine, University of GenevaINSERM U1212 Acides nucléiques: Régulations Naturelle et Artificielle (ARNA), Institut Européen de Chimie et Biologie, Université de BordeauxINSERM U1212 Acides nucléiques: Régulations Naturelle et Artificielle (ARNA), Institut Européen de Chimie et Biologie, Université de BordeauxINSERM U1212 Acides nucléiques: Régulations Naturelle et Artificielle (ARNA), Institut Européen de Chimie et Biologie, Université de BordeauxDepartment of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health; Key Laboratory of Infectious Diseases Research in South China (Ministry of Education), Southern Medical UniversityInstitute of Animal Science, Chinese Academy of Agricultural SciencesNational Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural UniversityDepartment of Microbiology and Molecular Medicine, University of GenevaNational Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural UniversityINSERM U1212 Acides nucléiques: Régulations Naturelle et Artificielle (ARNA), Institut Européen de Chimie et Biologie, Université de BordeauxDepartment of Microbiology and Molecular Medicine, University of GenevaBeijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical UniversityAbstract The phylum Apicomplexa comprises eukaryotic parasites that cause fatal diseases affecting millions of people and animals worldwide. Their mitochondrial genomes have been significantly reduced, leaving only three protein-coding genes and highly fragmented mitoribosomal rRNAs, raising challenging questions about mitoribosome composition, assembly and structure. Our study reveals how Toxoplasma gondii assembles over 40 mt-rRNA fragments using exclusively nuclear-encoded mitoribosomal proteins and three lineage-specific families of RNA-binding proteins. Among these are four proteins from the Apetala2/Ethylene Response Factor (AP2/ERF) family, originally known as transcription factors in plants and Apicomplexa, now repurposed as essential mitoribosome components. Cryo-EM analysis of the mitoribosome structure demonstrates how these AP2 proteins function as RNA binders to maintain mitoribosome integrity. The mitoribosome is also decorated with members of lineage-specific RNA-binding proteins belonging to RAP (RNA-binding domain abundant in Apicomplexa) proteins and HPR (heptatricopeptide repeat) families, highlighting the unique adaptations of these parasites. Solving the molecular puzzle of apicomplexan mitoribosome could inform the development of therapeutic strategies targeting organellar translation.https://doi.org/10.1038/s41467-024-55033-z
spellingShingle Chaoyue Wang
Sari Kassem
Rafael Eduardo Oliveira Rocha
Pei Sun
Tan-Trung Nguyen
Joachim Kloehn
Xianyong Liu
Lorenzo Brusini
Alessandro Bonavoglia
Sramona Barua
Fanny Boissier
Mayara Lucia Del Cistia
Hongjuan Peng
Xinming Tang
Fujie Xie
Zixuan Wang
Oscar Vadas
Xun Suo
Yaser Hashem
Dominique Soldati-Favre
Yonggen Jia
Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine
Nature Communications
title Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine
title_full Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine
title_fullStr Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine
title_full_unstemmed Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine
title_short Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine
title_sort apicomplexan mitoribosome from highly fragmented rrnas to a functional machine
url https://doi.org/10.1038/s41467-024-55033-z
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