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      Alternative Splicing in Apicomplexan Parasites

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          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.

          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 Plasmodium and Toxoplasma parasites, suggesting a biological role for at least some of the alternative splicing observed. Several studies have now disrupted conserved regulators of alternative splicing and demonstrated lethal effects in apicomplexans. This minireview discusses methods to accurately determine the extent of alternative splicing in Apicomplexa and discuss potential biological roles for this conserved process in a phylum of parasites with compact genomes.

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          Most cited references95

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          ToxoDB: an integrated Toxoplasma gondii database resource

          ToxoDB (http://ToxoDB.org) is a genome and functional genomic database for the protozoan parasite Toxoplasma gondii. It incorporates the sequence and annotation of the T. gondii ME49 strain, as well as genome sequences for the GT1, VEG and RH (Chr Ia, Chr Ib) strains. Sequence information is integrated with various other genomic-scale data, including community annotation, ESTs, gene expression and proteomics data. ToxoDB has matured significantly since its initial release. Here we outline the numerous updates with respect to the data and increased functionality available on the website.
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            Regulation of sexual development of Plasmodium by translational repression.

            G Mair (2006)
            Translational repression of messenger RNAs (mRNAs) plays an important role in sexual differentiation and gametogenesis in multicellular eukaryotes. Translational repression and mRNA turnover were shown to influence stage-specific gene expression in the protozoan Plasmodium. The DDX6-class RNA helicase, DOZI (development of zygote inhibited), is found in a complex with mRNA species in cytoplasmic bodies of female, blood-stage gametocytes. These translationally repressed complexes are normally stored for translation after fertilization. Genetic disruption of pbdozi inhibits the formation of the ribonucleoprotein complexes, and instead, at least 370 transcripts are diverted to a degradation pathway.
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              An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA.

              The 5' terminal sequences of several adenovirus 2 (Ad2) mRNAs, isolated late in infection, are complementary to sequences within the Ad2 genome which are remote from the DNA from which the main coding sequence of each mRNA is transcribed. This has been observed by forming RNA displacement loops (R loops) between Ad2 DNA and unfractionated polysomal RNA from infected cells. The 5' terminal sequences of mRNAs in R loops, variously located between positions 36 and 92, form complex secondary hybrids with single-stranded DNA from restriction endonuclease fragments containing sequences to the left of position 36 on the Ad2 genome. The structures visualized in the electron microscope show that short sequences coded at map positions 16.6, 19.6 and 26.6 on the R strand are joined to form a leader sequence of 150-200 nucleotides at the 5' end of many late mRNAs. A late mRNA which maps to the left of position 16.6 shows a different pattern of second site hybridization. It contains sequences from 4.9-6.0 linked directly to those from 9.6-10.9. These findings imply a new mechanism for the biosynthesis of Ad2 mRNA in mammalian cells.
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                Author and article information

                Contributors
                Role: Invited Editor
                Role: Editor
                Journal
                mBio
                MBio
                mbio
                mbio
                mBio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                19 February 2019
                Jan-Feb 2019
                : 10
                : 1
                : e02866-18
                Affiliations
                [a ]Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Australia
                [b ]School of BioSciences, The University of Melbourne, Parkville, Australia
                Washington University School of Medicine
                University of Texas Health Science Center at Houston
                Author notes
                Address correspondence to Stuart A. Ralph, saralph@ 123456unimelb.edu.au .
                Author information
                https://orcid.org/0000-0003-0114-7808
                Article
                mBio02866-18
                10.1128/mBio.02866-18
                6381282
                30782661
                c07424f5-7c86-4cd9-8132-a6199e62fee9
                Copyright © 2019 Yeoh et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 107, Pages: 15, Words: 9870
                Funding
                Funded by: Department of Health | National Health and Medical Research Council (NHMRC), https://doi.org/10.13039/501100000925;
                Award Recipient :
                Funded by: Department of Education and Training | Australian Research Council (ARC), https://doi.org/10.13039/501100000923;
                Award Recipient :
                Categories
                Minireview
                Host-Microbe Biology
                Custom metadata
                January/February 2019

                Life sciences
                plasmodium,rna splicing,toxoplasma,apicomplexan parasites,posttranscriptional control mechanisms

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