A putative RNA binding protein from <i>Plasmodium vivax</i> apicoplast

García‐Mauriño, Sofía; Díaz-Quintana, Antonio; Rivero-Rodríguez, Francisco; Cruz-Gallardo, Isabel; Grüttner, Christian; Hernández-Vellisca, Marian; Dı́az-Moreno, Irene

doi:10.1002/2211-5463.12351

Cited by 4 publications

(2 citation statements)

References 66 publications

(90 reference statements)

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“…Third, mutant FUS might directly compete with FMRP for 3'UTR binding. HuD 3'UTR contains multiple putative regulatory elements and competitive or cooperative 3'UTR binding is a regulatory mechanism extensively used by RBPs [52,53]. Interestingly, loss of the FMRP homolog dFXR leads to NMJ defects in Drosophila [54], while exogenous FMRP expression rescued NMJ and locomotor defects in a zebrafish FUS ALS model [14].…”

Section: Discussionmentioning

confidence: 99%

ALS-FUS mutation affects the activities of HuD/ELAVL4 and FMRP leading to axon phenotypes in motoneurons

Garone

Birsa

Rosito

et al. 2020

Preprint

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Mutations in RNA-binding proteins (RBPs) have been genetically associated with the motoneuron disease Amyotrophic Lateral Sclerosis (ALS). Using both human induced Pluripotent Stem Cells and mouse models, we found that FUS-ALS causative mutations have a profound impact on a network of RBPs, including two relevant factors with important roles in neuronal RNA metabolism: HuD and FMRP. Mechanistically, cytoplasmic localization of mutant FUS leads to upregulation of HuD levels through competition with FMRP for HuD 3’UTR binding. In turn, increased HuD levels overly stabilize the transcript levels of its targets, NRN1 and GAP43. As a consequence, mutant FUS motoneurons show altered axon branching and growth upon injury. Abnormal axon branching and regrowth in FUS mutant motoneurons could be rescued by dampening NRN1 levels. Since similar phenotypes have been previously described in SOD1 and TDP-43 mutant models, aberrant axonal growth and branching might represent broad early events in the pathogenesis of ALS.

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Section: Discussionmentioning

confidence: 99%

ALS-FUS mutation affects the activities of HuD/ELAVL4 and FMRP leading to axon phenotypes in motoneurons

Garone

Birsa

Rosito

et al. 2020

Preprint

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“…A number of nucleus‐encoded, apicoplast‐targeted proteins have been identified, which may function in RNA processing. Only one RNA‐binding protein ( Plasmodium vivax PVX_084415 ) has been partially characterized, although the stability of the heterologously expressed protein was such that it was not possible to carry out functional assays, though it did bind to uridine‐rich RNA (García‐Mauriño et al, ). The insoluble nature of both heterologously expressed Plasmodium proteins (Mehlin et al, ) and PPR proteins (Manna, ; Rackham & Filipovska, ) has impeded characterization of their structure and function.…”

Section: Introductionmentioning

confidence: 99%

An essential pentatricopeptide repeat protein in the apicomplexan remnant chloroplast

Hicks

Lassadi

Carpenter

et al. 2019

Cellular Microbiology

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The malaria parasite Plasmodium and other apicomplexans such as Toxoplasma evolved from photosynthetic organisms and contain an essential, remnant plastid termed the apicoplast. Transcription of the apicoplast genome is polycistronic with extensive RNA processing. Yet little is known about the mechanism of apicoplast RNA processing. In plants, chloroplast RNA processing is controlled by multiple pentatricopeptide repeat (PPR) proteins. Here, we identify the single apicoplast PPR protein, PPR1. We show that the protein is essential and that it binds to RNA motifs corresponding with previously characterized processing sites. Additionally, PPR1 shields RNA transcripts from ribonuclease degradation. This is the first characterization of a PPR protein from a nonphotosynthetic plastid.

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A proteomic glimpse into the effect of antimalarial drugs onPlasmodium falciparumproteome towards highlighting possible therapeutic targets

Dousti

Manzano-Román

Rashidi

et al. 2020

Pathogens and Disease

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There is no effective vaccine against malaria; therefore, chemotherapy is to date only choice to fight against this infectious disease. However, there are growing evidences of drug-resistance mechanisms in malaria treatments. Therefore, the identification of new drug targets is an urgent need for the clinic management of the disease. Proteomic approaches offer the chance of determining the effects of antimalarial drugs on the proteome of Plasmodium parasites. Accordingly, we here review the effects of antimalarial drugs on Plasmodium falciparum proteome pointing out the relevance of several proteins as possible drug targets in malaria treatment. In addition, some of the P. falciparum stage-specific altered proteins and parasite-host interactions might play important roles in pathogenicity, survival, invasion, and metabolic pathways and thus serve as potential source of drug targets. In this review, we have identified several proteins including thioredoxin reductase, helicases, peptidyl-prolyl cis-trans isomerase, endoplasmic reticulum-resident calcium-binding protein, choline/ethanolamine phosphotransferase, purine nucleoside phosphorylase, apical membrane antigen 1, glutamate dehydrogenase, hypoxanthine guanine phosphoribosyl transferase, heat shock protein70x, knob-associated histidine-rich protein, and erythrocyte membrane protein 1 as promising antimalarial drugs targets. Overall, proteomic approaches are able to partially facilitate finding the possible drug targets. However, the integration of other ‘omics’ and specific pharmaceutical techniques with proteomics may increase the therapeutic properties of the critical proteins identified in P. falciparum proteome.

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A putative RNA binding protein from Plasmodium vivax apicoplast

Cited by 4 publications

References 66 publications

ALS-FUS mutation affects the activities of HuD/ELAVL4 and FMRP leading to axon phenotypes in motoneurons

ALS-FUS mutation affects the activities of HuD/ELAVL4 and FMRP leading to axon phenotypes in motoneurons

An essential pentatricopeptide repeat protein in the apicomplexan remnant chloroplast

A proteomic glimpse into the effect of antimalarial drugs onPlasmodium falciparumproteome towards highlighting possible therapeutic targets

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