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Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23
Journal article   Open access   Peer reviewed

Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23

Swati Dass, Michael Mather, Joanne Morrisey, Liqin Ling, Akhil Vaidya and Hangjun Ke
PloS one, v 17(10), pe0274993
01 Oct 2022
DOI: https://doi.org/10.1371/journal.pone.0274993
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0274993View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Antimalarial agents Assembly Atovaquone Cloning CRISPR Cytochrome Cytochrome bc1 Cytochromes Deoxyribonucleic acid DNA E coli Gene sequencing Genomes Malaria Metabolic pathways Mitochondrial DNA Organisms Parasites Plasmids Plasmodium Plasmodium falciparum Proteins Ribonucleic acid Ribosomal proteins RNA rRNA Therapeutic targets Transcriptomics Vector-borne diseases
The mitochondrion of malaria parasites is an attractive antimalarial drug target, which require mitoribosomes to translate genes encoded in the mitochondrial (mt) DNA. Plasmodium mitoribosomes are composed of highly fragmented ribosomal RNA (rRNA) encoded in the mtDNA. All mitoribosomal proteins (MRPs) and other assembly factors are encoded in the nuclear genome. Here, we have studied one putative assembly factor, RSM22 (Pf3D7_1027200) and one large subunit (LSU) MRP, L23 (Pf3D7_1239100) in Plasmodium falciparum. We show that both proteins localize to the mitochondrion. Conditional knock down (KD) of PfRSM22 or PfMRPL23 leads to reduced cytochrome bc1 complex activity and increased sensitivity to bc1 inhibitors such as atovaquone and ELQ-300. Using RNA sequencing as a tool, we reveal the transcriptomic changes of nuclear and mitochondrial genomes upon KD of these two proteins. In the early phase of KD, while most mt rRNAs and transcripts of putative MRPs were downregulated in the absence of PfRSM22, many mt rRNAs and several MRPs were upregulated after KD of PfMRPL23. The contrast effects in the early phase of KD likely suggests non-redundant roles of PfRSM22 and PfMRPL23 in the assembly of P. falciparum mitoribosomes. At the late time points of KD, loss of PfRSM22 and PfMRPL23 caused defects in many essential metabolic pathways and transcripts related to essential mitochondrial functions, leading to parasite death. In addition, we enlist mitochondrial proteins of unknown function that are likely novel Plasmodium MRPs based on their structural similarity to known MRPs as well as their expression profiles in KD parasites.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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