Polypeptide release factors and stop codon recognition in the apicoplast and mitochondrion of <i>Plasmodium falciparum</i>

Vaishya, Suniti; Kumar, Vikash; Gupta, Ankit; Siddiqi, Mohammad Imran; Habib, Saman

doi:10.1111/mmi.13369

Cited by 13 publications

(7 citation statements)

References 71 publications

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“…While ArfB forms an mRNA-stabilizing homodimer, the other rescue pathways are not known to involve dimer formation. Isolated mitochondrial homolog ICT1 was reported to dimerize in solution 56 , but it remains to be shown whether ICT1 dimerizes to rescue stalled mitochondrial ribosomes. Cryo-EM structure of Dom34 bound the 80S ribosome with a poly-A-containing mRNA did not resolve mRNA beyond the P-site codon 52 , suggesting that Dom34 can efficiently outcompete mRNA that can stochastically leave the mRNA tunnel.…”

Section: Resultsmentioning

confidence: 99%

ArfB can displace mRNA to rescue stalled ribosomes

et al. 2020

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Ribosomes stalled during translation must be rescued to replenish the pool of translation-competent ribosomal subunits. Bacterial alternative rescue factor B (ArfB) releases nascent peptides from ribosomes stalled on mRNAs truncated at the A site, allowing ribosome recycling. Prior structural work revealed that ArfB recognizes such ribosomes by inserting its C-terminal α-helix into the vacant mRNA tunnel. In this work, we report that ArfB can efficiently recognize a wider range of mRNA substrates, including longer mRNAs that extend beyond the A-site codon. Single-particle cryo-EM unveils that ArfB employs two modes of function depending on the mRNA length. ArfB acts as a monomer to accommodate a shorter mRNA in the ribosomal A site. By contrast, longer mRNAs are displaced from the mRNA tunnel by more than 20 Å and are stabilized in the intersubunit space by dimeric ArfB. Uncovering distinct modes of ArfB function resolves conflicting biochemical and structural studies, and may lead to re-examination of other ribosome rescue pathways, whose functions depend on mRNA lengths.

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Section: Resultsmentioning

confidence: 99%

ArfB can displace mRNA to rescue stalled ribosomes

et al. 2020

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“…Thus, this study is a major expansion of the available data on avian haemosporidian parasites. Haemosporidian mitochondrial genes are translated, but the actual mechanism is unclear ( Vaidya and Mather 2009 ; Habib et al 2016 ; Vaishya et al 2016 ). Although this extended data set allowed documentation of putative initiation codons on mtDNA genes, those are still uncertain in cox1 and cox3 .…”

Section: Resultsmentioning

confidence: 99%

Mode and Rate of Evolution of Haemosporidian Mitochondrial Genomes: Timing the Radiation of Avian Parasites

Pacheco

Matta

Valkiūnas

et al. 2017

Molecular Biology and Evolution

141

148

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Haemosporidians are a diverse group of vector-borne parasitic protozoa that includes the agents of human malaria; however, most of the described species are found in birds and reptiles. Although our understanding of these parasites’ diversity has expanded by analyses of their mitochondrial genes, there is limited information on these genes’ evolutionary rates. Here, 114 mitochondrial genomes (mtDNA) were studied from species belonging to four genera: Leucocytozoon, Haemoproteus, Hepatocystis, and Plasmodium. Contrary to previous assertions, the mtDNA is phylogenetically informative. The inferred phylogeny showed that, like the genus Plasmodium, the Leucocytozoon and Haemoproteus genera are not monophyletic groups. Although sensitive to the assumptions of the molecular dating method used, the estimated times indicate that the diversification of the avian haemosporidian subgenera/genera took place after the Cretaceous–Paleogene boundary following the radiation of modern birds. Furthermore, parasite clade differences in mtDNA substitution rates and strength of negative selection were detected. These differences may affect the biological interpretation of mtDNA gene lineages used as a proxy to species in ecological and parasitological investigations. Given that the mitochondria are critically important in the parasite life cycle stages that take place in the vector and that the transmission of parasites belonging to particular clades has been linked to specific insect families/subfamilies, this study suggests that differences in vectors have affected the mode of evolution of haemosporidian mtDNA genes. The observed patterns also suggest that the radiation of haemosporidian parasites may be the result of community-level evolutionary processes between their vertebrate and invertebrate hosts.

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“…Similar to P. falciparum, no initiation factors are encoded by the apicoplast genome and therefore are likely to be encoded by the nuclear genome and then recruited to the apicoplast (Haider et al, 2015). Translation termination is achieved by a single release factor, PfRF2 Api , which displays specific recognition of both UAA and UGA, the only two stop codons found in apicoplast ORFs (Vaishya et al, 2016). Interestingly, of the 38 ORFs encoded by the apicoplast genome of B. duncani, 35 carry a UAA stop codon, two (rps3 and the rpl36) carry a UGA stop codon, and one (HypN) ends with the UAG stop codon.…”

Section: Annotation Of the Apicoplast Genome Of B Duncanimentioning

confidence: 99%

Insights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes

Virji

Lawres

et al. 2019

International Journal for Parasitology

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Babesia microti and Babesia duncani are the main causative agents of human babesiosis in the United States. While significant knowledge about B. microti has been gained over the past few years, nothing is known about B. duncani biology, pathogenesis, mode of transmission or sensitivity to currently recommended therapies. Studies in immunocompetent wild type mice and hamsters have shown that unlike B. microti, infection with B. duncani results in severe pathology and ultimately death. The parasite factors involved in B. duncani virulence remain unknown. Here we report the first known completed sequence and annotation of the apicoplast and mitochondrial genomes of B. duncani. We found that the apicoplast genome of this parasite consists of a 34 kb monocistronic circular molecule encoding functions that are important for apicoplast gene transcription as well as translation and maturation of the organelle's proteins. The mitochondrial genome of B. duncani consists of a 5.9 kb monocistronic linear molecule with two inverted repeats of 48 bp at both ends. Using the conserved cytochrome b (Cytb) and cytochrome c oxidase subunit I (coxI) proteins encoded by the mitochondrial genome, phylogenetic analysis revealed that B. duncani defines a new lineage among apicomplexan parasites distinct from B. microti, Babesia bovis, Theileria spp. and Plasmodium spp. Annotation of the apicoplast and mitochondrial genomes of B. duncani identified targets for development of effective therapies. Our studies set the stage for evaluation of the efficacy of these drugs alone or in combination against B. duncani in culture as well as in animal models.

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Polypeptide release factors and stop codon recognition in the apicoplast and mitochondrion of Plasmodium falciparum

Cited by 13 publications

References 71 publications

ArfB can displace mRNA to rescue stalled ribosomes

ArfB can displace mRNA to rescue stalled ribosomes

Mode and Rate of Evolution of Haemosporidian Mitochondrial Genomes: Timing the Radiation of Avian Parasites

Insights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes

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