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Alternative splicing mechanisms orchestrating post-transcriptional gene expression: intron retention and the intron-rich genome of apicomplexan parasites

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Abstract

Apicomplexan parasites including Toxoplasma gondii and Plasmodium species have complex life cycles that include multiple hosts and differentiation through several morphologically distinct stages requiring marked changes in gene expression. This review highlights emerging evidence implicating regulation of mRNA splicing as a mechanism to prime these parasites for rapid gene expression upon differentiation. We summarize the most important insights in alternative splicing including its role in regulating gene expression by decreasing mRNA abundance via ‘Regulated Unproductive Splicing and Translation’. As a related but less well-understood mechanism, we discuss also our recent work suggesting a role for intron retention for precluding translation of stage specific isoforms of T. gondii glycolytic enzymes. We additionally provide new evidence that intron retention might be a widespread mechanism during parasite differentiation. Supporting this notion, recent genome-wide analysis of Toxoplasma and Plasmodium suggests intron retention is more pervasive than heretofore thought. These findings parallel recent emergence of intron retention being more prevalent in mammals than previously believed, thereby adding to the established roles in plants, fungi and unicellular eukaryotes. Deeper mechanistic studies of intron retention will provide important insight into its role in regulating gene expression in apicomplexan parasites and more general in eukaryotic organisms.

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Acknowledgments

We thank Dr. My-Hang (Mae) Huynh for helpful discussions and editorial assistance. This work was supported by Fondazione Cassa di Risparmio di Perugia, Grant No. 2014.0222.021. Studies in the Carruthers lab are supported by grants from the Stanley Medical Research Institute (07R11857 and N017229) and the US National Institutes of Health (AI116416, and AI46675).

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Authors and Affiliations

  1. Department of Chemistry, Biology and Biotechnology, University of Perugia, via del Giochetto, 06122, Perugia, Italy

    Matteo Lunghi, Alessandro Magini, Carla Emiliani & Manlio Di Cristina

  2. Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy

    Furio Spano

  3. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA

    Vern B. Carruthers

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  1. Matteo Lunghi
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  2. Furio Spano
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  3. Alessandro Magini
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  4. Carla Emiliani
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  5. Vern B. Carruthers
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  6. Manlio Di Cristina
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Correspondence to Manlio Di Cristina.

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Communicated by M. Kupiec.

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Lunghi, M., Spano, F., Magini, A. et al. Alternative splicing mechanisms orchestrating post-transcriptional gene expression: intron retention and the intron-rich genome of apicomplexan parasites. Curr Genet 62, 31–38 (2016). https://doi.org/10.1007/s00294-015-0506-x

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