Browsing by Subject "Eukaryota"

Now showing 1 - 5 of 5
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    Epitranscriptomics in parasitic protists: Role of RNA chemical modifications in posttranscriptional gene regulation
    (Public Library of Science, 2022-12-22) Catacalos, Cassandra; Krohannon, Alexander; Somalraju, Sahiti; Meyer, Kate D.; Janga, Sarath Chandra; Chakrabarti, Kausik; BioHealth Informatics, School of Informatics and Computing
    "Epitranscriptomics" is the new RNA code that represents an ensemble of posttranscriptional RNA chemical modifications, which can precisely coordinate gene expression and biological processes. There are several RNA base modifications, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ), etc. that play pivotal roles in fine-tuning gene expression in almost all eukaryotes and emerging evidences suggest that parasitic protists are no exception. In this review, we primarily focus on m6A, which is the most abundant epitranscriptomic mark and regulates numerous cellular processes, ranging from nuclear export, mRNA splicing, polyadenylation, stability, and translation. We highlight the universal features of spatiotemporal m6A RNA modifications in eukaryotic phylogeny, their homologs, and unique processes in 3 unicellular parasites-Plasmodium sp., Toxoplasma sp., and Trypanosoma sp. and some technological advances in this rapidly developing research area that can significantly improve our understandings of gene expression regulation in parasites.
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    Intrinsic Disorder Is a Common Feature of Hub Proteins from Four Eukaryotic Interactomes
    (PLOS, 2006-08-04) Haynes, Chad; Oldfield, Christopher J.; Ji, Fei; Klitgord, Niels; Cusick, Michael E.; Radivojac, Predrag; Uversky, Vladimir N.; Vidal, Marc; Iakoucheva, Lilia M.; Biochemistry and Molecular Biology, School of Medicine
    Recent proteome-wide screening approaches have provided a wealth of information about interacting proteins in various organisms. To test for a potential association between protein connectivity and the amount of predicted structural disorder, the disorder propensities of proteins with various numbers of interacting partners from four eukaryotic organisms (Caenorhabditis elegans, Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens) were investigated. The results of PONDR VL-XT disorder analysis show that for all four studied organisms, hub proteins, defined here as those that interact with ≥10 partners, are significantly more disordered than end proteins, defined here as those that interact with just one partner. The proportion of predicted disordered residues, the average disorder score, and the number of predicted disordered regions of various lengths were higher overall in hubs than in ends. A binary classification of hubs and ends into ordered and disordered subclasses using the consensus prediction method showed a significant enrichment of wholly disordered proteins and a significant depletion of wholly ordered proteins in hubs relative to ends in worm, fly, and human. The functional annotation of yeast hubs and ends using GO categories and the correlation of these annotations with disorder predictions demonstrate that proteins with regulation, transcription, and development annotations are enriched in disorder, whereas proteins with catalytic activity, transport, and membrane localization annotations are depleted in disorder. The results of this study demonstrate that intrinsic structural disorder is a distinctive and common characteristic of eukaryotic hub proteins, and that disorder may serve as a determinant of protein interactivity.
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    Molecular tools for analysis of gene function in parasitic microorganisms
    (Springer, 2007) Meissner, Markus; Agop-Nersesian, Carolina; Sullivan, William J., Jr.; Pharmacology and Toxicology, School of Medicine
    With the completion of several genome sequences for parasitic protozoa, research in molecular parasitology entered the "post-genomic" era. Accompanied by global transcriptome and proteome analysis, huge datasets have been generated that have added many novel candidates to the list of drug and vaccine targets. The challenge is now to validate these factors and to bring science back to the bench to perform a detailed characterization. In some parasites, like Trypanosoma brucei, high-throughput genetic screens have been established using RNA interference [for a detailed review, see Motyka and Englund (2004)]. In most protozoan parasites, however, more time-consuming approaches have to be employed to identify and characterize the function of promising candidates in detail. This review aims to summarize the status of molecular genetic tools available for a variety of protozoan pathogens and discuss how they can be implemented to advance our understanding of parasite biology.
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    Protein control of membrane and organelle dynamics: Insights from the divergent eukaryote Toxoplasma gondii
    (Elsevier, 2022) Ovciarikova, Jana; Oliveira Souza, Rodolpho Ornitz; Arrizabalaga, Gustavo; Sheiner, Lilach; Pharmacology and Toxicology, School of Medicine
    Integral membrane protein complexes control key cellular functions in eukaryotes by defining membrane-bound spaces within organelles and mediating inter-organelles contacts. Despite the critical role of membrane complexes in cell biology, most of our knowledge is from a handful of model systems, primarily yeast and mammals, while a full functional and evolutionary understanding remains incomplete without the perspective from a broad range of divergent organisms. Apicomplexan parasites are single-cell eukaryotes whose survival depends on organelle compartmentalisation and communication. Studies of a model apicomplexan, Toxoplasma gondii, reveal unexpected divergence in the composition and function of complexes previously considered broadly conserved, such as the mitochondrial ATP synthase and the tethers mediating ER-mitochondria membrane contact sites. Thus, Toxoplasma joins the repertoire of divergent model eukaryotes whose research completes our understanding of fundamental cell biology.
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    Stress response pathways in protozoan parasites
    (Wiley, 2008) Vonlaufen, Nathalie; Kanzok, Stefan M.; Wek, Ronald C.; Sullivan, William J., Jr.; Pharmacology and Toxicology, School of Medicine
    Diseases caused by protozoan parasites have a dramatic impact on world health. Emerging drug resistance and a general lack of experimental understanding has created a void in the medicine cabinet used to treat these widespread infections. A novel therapeutic idea that is receiving more attention is centred on targeting the microbe's response to the multitude of environmental stresses it encounters. Protozoan pathogens have complex life cycles, often having to transition from one host to another, or survive in a cyst form in the environment until a new host arrives. The need to respond to environmental cues and stress, and endure in less than optimal conditions, is paramount to their viability and successful progression through their life cycle. This review summarizes the research on parasitic stress responses for Apicomplexa, kinetoplastids and anaerobic protozoa, with an eye towards how these processes may be exploited therapeutically.