Protein–RNA interactions important for Plasmodium transmission

Rios, Kelly T.; Lindner, Scott E.

doi:10.1371/journal.ppat.1008095

Cited by 17 publications

(19 citation statements)

References 51 publications

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“…In P. falciparum , Puf2 from the PUF-family of proteins binds to mRNA targets like P25 and P28 and the resulting disruption of the puf2 gene enhances gametocytogenesis with an increase in number of male gametocytes [ 88 , 89 ]. Plasmodium expresses a large number of RNA-binding proteins, and the disruption of appropriate protein-RNA interactions and their trafficking can indeed serve as possible targets to arrest transmission [ 90 , 91 ].…”

Section: Understanding P Falciparum Gametocytementioning

confidence: 99%

Targeting Gametocytes of the Malaria Parasite Plasmodium falciparum in a Functional Genomics Era: Next Steps

2021

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Mosquito transmission of the deadly malaria parasite Plasmodium falciparum is mediated by mature sexual forms (gametocytes). Circulating in the vertebrate host, relatively few intraerythrocytic gametocytes are picked up during a bloodmeal to continue sexual development in the mosquito vector. Human-to-vector transmission thus represents an infection bottleneck in the parasite’s life cycle for therapeutic interventions to prevent malaria. Even though recent progress has been made in the identification of genetic factors linked to gametocytogenesis, a plethora of genes essential for sexual-stage development are yet to be unraveled. In this review, we revisit P. falciparum transmission biology by discussing targetable features of gametocytes and provide a perspective on a forward-genetic approach for identification of novel transmission-blocking candidates in the future.

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Section: Understanding P Falciparum Gametocytementioning

confidence: 99%

Targeting Gametocytes of the Malaria Parasite Plasmodium falciparum in a Functional Genomics Era: Next Steps

2021

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“…The uis3 gene represents another potential liver stage target and is conserved across human, primate and rodent Plasmodium species. It is actively transcribed in sporozoites but translationally repressed until the parasite infects hepatocytes (66). Mice immunized with PfUIS3 and challenged with P. berghei sporozoites exhibited a significant delay in the time to patent parasitemia (65).…”

Section: Pre-erythrocytic Targetsmentioning

confidence: 99%

The Case for Exploiting Cross-Species Epitopes in Malaria Vaccine Design

Mitran

Yanow

2020

Front. Immunol.

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The infection dynamics between different species of Plasmodium that infect the same human host can both suppress and exacerbate disease. This could arise from inter-parasite interactions, such as competition, from immune regulation, or both. The occurrence of protective, cross-species (heterologous) immunity is an unlikely event, especially considering that strain-transcending immunity within a species is only partial despite lifelong exposure to that species. Here we review the literature in humans and animal models to identify the contexts where heterologous immunity can arise, and which antigens may be involved. From the perspective of vaccine design, understanding the mechanisms by which exposure to an antigen from one species can elicit a protective response to another species offers an alternative strategy to conventional approaches that focus on immunodominant antigens within a single species. The underlying hypothesis is that certain epitopes are conserved across evolution, in sequence or in structure, and shared in antigens from different species. Vaccines that focus on conserved epitopes may overcome the challenges posed by polymorphic immunodominant antigens; but to uncover these epitopes requires approaches that consider the evolutionary history of protein families across species. The key question for vaccinologists will be whether vaccines that express these epitopes can elicit immune responses that are functional and contribute to protection against Plasmodium parasites.

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“…No reuse allowed without permission. (Vembar et al 2016;Painter et al 2018;Rios and Lindner 2019). For example, a plant-like transcription factor family consisting of 27-members, known as Apicomplexan AP2 (ApiAP2) protein family, expressed in different stages during malaria parasite development, is critically involved in parasite development and differentiation processes (Balaji et al 2005;Painter et al 2018).…”

Section: Structural Rnasmentioning

confidence: 99%

“…A , ApiAP2 (PF3D7_0420300) expressing protein is known to functionally interact with ACACACAT DNA motif for P. falciparum gene expression regulation (Toenhake et al 2018) and its expression is correlated with drug resistance transporter, pfCRT, indicating potential role in resistance evolution to chemotherapeutic molecules in malaria (Siwo et al 2015). Similarly, for RNA mediated post transcriptional gene regulation, RNA binding proteins (RBPs) in P. falciparum plays pivotal role in translational regulation (Bunnik et al 2016;Rios and Lindner 2019). Our duplex RNA-seq data revealed strong accumulation of base-paired reads mapping to DNA/RNA binding factor PfAlba3 (PF3D7_1006200) ( Figure 4C).…”

Section: Structural Rnasmentioning

confidence: 99%

“…In addition, several studies have indicated that post-transcriptional control mechanisms are major means of gene expression regulation in malaria parasites in both sexual and asexual stages. Global ribosome profiling, mechanistic studies on RNA binding proteins (RBPs) (Mair et al 2006;Sims et al 2009;Mair et al 2010;Otto et al 2010;Caro et al 2014;Zhang et al 2014b;Lu et al 2017;Rios and Lindner 2019) and differential gene expression studies have shown that a wide array of genes, including virulence genes in malaria parasites, are regulated at both posttranscriptional and translational level (Amulic et al 2009;Amit-Avraham et al 2015;Chan et al 2017). RNA-binding proteins (RBPs) are abundant in P. falciparum and could particularly influence post -transcriptional genetic control cascades in malaria (Bunnik et al 2013;Reddy et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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The RNA Structurome in the Asexual Blood Stages of Malaria PathogenPlasmodium falciparum

Alvarez

Ospina

Dey

et al. 2020

Preprint

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RNA as an effector of biological functions often adopts secondary and tertiary structural folds. Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and noncoding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis, combining high-throughput nuclease mapping of RNA structures by duplex RNA-seq, immunoaffinity purification and RNA analysis, collectively measured differentially base-paired RNA regions during the parasite development. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, ~71% of the genes with secondary structures are found to be protein coding mRNAs. Mapping pattern of these base-paired RNAs corresponded to all portions of protein-coding mRNAs, including 5- UTR, CDS and 3- UTR. In addition to histone family genes which are known to form secondary structures in their mRNAs, transcripts from genes which are important for transcriptional and post-transcriptional control, such as unique plant-like transcription factor family, ApiAP2, DNA/RNA binding protein family, Alba, ribosomal proteins and eukaryotic initiation factors involved in translational control and the ones important for RBC invasion and cytoadherence also show strong accumulation of duplex RNA reads in various asexual stages. Intriguingly, our study determined a positive relationship between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs.

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Protein–RNA interactions important for Plasmodium transmission

Cited by 17 publications

References 51 publications

Targeting Gametocytes of the Malaria Parasite Plasmodium falciparum in a Functional Genomics Era: Next Steps

Targeting Gametocytes of the Malaria Parasite Plasmodium falciparum in a Functional Genomics Era: Next Steps

The Case for Exploiting Cross-Species Epitopes in Malaria Vaccine Design

The RNA Structurome in the Asexual Blood Stages of Malaria PathogenPlasmodium falciparum

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