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  1. Article ; Online: Characterisation of the OTU domain deubiquitinase complement of

    Wilde, Mary-Louise / Ruparel, Ushma / Klemm, Theresa / Lee, V Vern / Calleja, Dale J / Komander, David / Tonkin, Christopher J

    Life science alliance

    2023  Volume 6, Issue 6

    Abstract: The phylum Apicomplexa contains several parasitic species of medical and agricultural importance. The ubiquitination machinery remains, for the most part, uncharacterised in apicomplexan parasites, despite the important roles that it plays in eukaryotic ... ...

    Abstract The phylum Apicomplexa contains several parasitic species of medical and agricultural importance. The ubiquitination machinery remains, for the most part, uncharacterised in apicomplexan parasites, despite the important roles that it plays in eukaryotic biology. Bioinformatic analysis of the ubiquitination machinery in apicomplexan parasites revealed an expanded ovarian tumour domain-containing (OTU) deubiquitinase (DUB) family in
    MeSH term(s) Toxoplasma/genetics ; Toxoplasma/metabolism ; Ubiquitin/genetics ; Ubiquitin/metabolism ; Ubiquitination ; Plasmodium ; Deubiquitinating Enzymes/genetics ; Deubiquitinating Enzymes/metabolism
    Chemical Substances Ubiquitin ; Deubiquitinating Enzymes (EC 3.4.19.12)
    Language English
    Publishing date 2023-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202201710
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Direct Nanopore Sequencing of mRNA Reveals Landscape of Transcript Isoforms in Apicomplexan Parasites.

    Lee, V Vern / Judd, Louise M / Jex, Aaron R / Holt, Kathryn E / Tonkin, Christopher J / Ralph, Stuart A

    mSystems

    2021  Volume 6, Issue 2

    Abstract: Alternative splicing is a widespread phenomenon in metazoans by which single genes are able to produce multiple isoforms of the gene product. However, this has been poorly characterized in apicomplexans, a major phylum of some of the most important ... ...

    Abstract Alternative splicing is a widespread phenomenon in metazoans by which single genes are able to produce multiple isoforms of the gene product. However, this has been poorly characterized in apicomplexans, a major phylum of some of the most important global parasites. Efforts have been hampered by atypical transcriptomic features, such as the high AU content of
    Language English
    Publishing date 2021-03-09
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN 2379-5077
    DOI 10.1128/mSystems.01081-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Alternative Splicing in Apicomplexan Parasites.

    Yeoh, Lee M / Lee, V Vern / McFadden, Geoffrey I / Ralph, Stuart A

    mBio

    2019  Volume 10, Issue 1

    Abstract: Alternative splicing is a widespread, essential, and complex component of gene regulation. Apicomplexan parasites have long been recognized to produce alternatively spliced transcripts for some genes and can produce multiple protein products that are ... ...

    Abstract Alternative splicing is a widespread, essential, and complex component of gene regulation. Apicomplexan parasites have long been recognized to produce alternatively spliced transcripts for some genes and can produce multiple protein products that are essential for parasite growth. Recent approaches are now providing more wide-ranging surveys of the extent of alternative splicing; some indicate that alternative splicing is less widespread than in other model eukaryotes, whereas others suggest levels comparable to those of previously studied groups. In many cases, apicomplexan alternative splicing events appear not to generate multiple alternative proteins but instead produce aberrant or noncoding transcripts. Nonetheless, appropriate regulation of alternative splicing is clearly essential in
    MeSH term(s) Alternative Splicing ; Animals ; Apicomplexa/genetics ; Gene Expression Regulation ; Parasites/genetics
    Language English
    Publishing date 2019-02-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.02866-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Alternative splicing is required for stage differentiation in malaria parasites

    Yeoh, Lee M / Goodman, Christopher D / Mollard, Vanessa / McHugh, Emma / Lee, V. Vern / Sturm, Angelika / Cozijnsen, Anton / McFadden, Geoffrey I / Ralph, Stuart A

    Genome biology. 2019 Dec., v. 20, no. 1

    2019  

    Abstract: BACKGROUND: In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life cycles. The role of alternative ... ...

    Abstract BACKGROUND: In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life cycles. The role of alternative splicing in transitions between cell types and establishing cellular identity is currently unknown in any unicellular organism. RESULTS: To test whether alternative splicing in unicellular protists plays a role in cellular differentiation, we conduct RNA-seq to compare splicing in female and male sexual stages to asexual intraerythrocytic stages in the rodent malaria parasite Plasmodium berghei. We find extensive changes in alternative splicing between stages and a role for alternative splicing in sexual differentiation. Previously, general gametocyte differentiation was shown to be modulated by specific transcription factors. Here, we show that alternative splicing establishes a subsequent layer of regulation, controlling genes relating to consequent sex-specific differentiation of gametocytes. CONCLUSIONS: We demonstrate that alternative splicing is reprogrammed during cellular differentiation of a unicellular protist. Disruption of an alternative splicing factor, PbSR-MG, perturbs sex-specific alternative splicing and decreases the ability of the parasites to differentiate into male gametes and oocysts, thereby reducing transmission between vertebrate and insect hosts. Our results reveal alternative splicing as an integral, stage-specific phenomenon in these protists and as a regulator of cellular differentiation that arose early in eukaryotic evolution.
    Keywords Plasmodium berghei ; alternative splicing ; cell differentiation ; evolution ; females ; gametocytes ; genes ; hosts ; insects ; malaria ; males ; oocysts ; parasites ; protists ; rodents ; sequence analysis ; sexual development ; transcription factors
    Language English
    Dates of publication 2019-12
    Size p. 151.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6906
    ISSN (online) 1474-760X
    ISSN 1465-6906
    DOI 10.1186/s13059-019-1756-6
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Chromosome-level genome of Schistosoma haematobium underpins genome-wide explorations of molecular variation.

    Stroehlein, Andreas J / Korhonen, Pasi K / Lee, V Vern / Ralph, Stuart A / Mentink-Kane, Margaret / You, Hong / McManus, Donald P / Tchuenté, Louis-Albert Tchuem / Stothard, J Russell / Kaur, Parwinder / Dudchenko, Olga / Aiden, Erez Lieberman / Yang, Bicheng / Yang, Huanming / Emery, Aidan M / Webster, Bonnie L / Brindley, Paul J / Rollinson, David / Chang, Bill C H /
    Gasser, Robin B / Young, Neil D

    PLoS pathogens

    2022  Volume 18, Issue 2, Page(s) e1010288

    Abstract: Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital ... ...

    Abstract Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover 'new' genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation within S. haematobium among some geographical locations in Africa revealed unique genomic 'signatures' that matched species other than S. haematobium, indicating the occurrence of introgression events. The present reference genome (designated Shae.V3) and the findings from this study solidly underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved and sustained control of urogenital schistosomiasis.
    MeSH term(s) Animals ; Chromosomes/parasitology ; Genes, Protozoan ; Genetic Variation ; Genome ; Genome, Protozoan ; Genome-Wide Association Study ; Schistosoma haematobium/genetics ; Schistosomiasis haematobia/parasitology ; Sequence Analysis, DNA ; Transcriptome
    Language English
    Publishing date 2022-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010288
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Alternative splicing is required for stage differentiation in malaria parasites.

    Yeoh, Lee M / Goodman, Christopher D / Mollard, Vanessa / McHugh, Emma / Lee, V Vern / Sturm, Angelika / Cozijnsen, Anton / McFadden, Geoffrey I / Ralph, Stuart A

    Genome biology

    2019  Volume 20, Issue 1, Page(s) 151

    Abstract: Background: In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life cycles. The role of alternative ... ...

    Abstract Background: In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life cycles. The role of alternative splicing in transitions between cell types and establishing cellular identity is currently unknown in any unicellular organism.
    Results: To test whether alternative splicing in unicellular protists plays a role in cellular differentiation, we conduct RNA-seq to compare splicing in female and male sexual stages to asexual intraerythrocytic stages in the rodent malaria parasite Plasmodium berghei. We find extensive changes in alternative splicing between stages and a role for alternative splicing in sexual differentiation. Previously, general gametocyte differentiation was shown to be modulated by specific transcription factors. Here, we show that alternative splicing establishes a subsequent layer of regulation, controlling genes relating to consequent sex-specific differentiation of gametocytes.
    Conclusions: We demonstrate that alternative splicing is reprogrammed during cellular differentiation of a unicellular protist. Disruption of an alternative splicing factor, PbSR-MG, perturbs sex-specific alternative splicing and decreases the ability of the parasites to differentiate into male gametes and oocysts, thereby reducing transmission between vertebrate and insect hosts. Our results reveal alternative splicing as an integral, stage-specific phenomenon in these protists and as a regulator of cellular differentiation that arose early in eukaryotic evolution.
    MeSH term(s) Alternative Splicing ; Animals ; Germ Cells/metabolism ; Life Cycle Stages/genetics ; Mice ; Plasmodium berghei/genetics ; Plasmodium berghei/growth & development ; Plasmodium berghei/metabolism ; Transcription, Genetic
    Language English
    Publishing date 2019-08-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6906
    ISSN (online) 1474-760X
    ISSN 1465-6906
    DOI 10.1186/s13059-019-1756-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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