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Illuminating the mechanism of monogenic antigen expression in trypanosomes

Nature Reviews Microbiology volume 19, page 746 (2021)Cite this article

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This month’s Under the Lens discusses how recent advances in understanding the spatial integration of transcription and splicing sites have shed light on the mechanism that ensures monogenic antigen expression in trypanosomes.

To maintain persistent infections, parasites must evade the immune response of the host. In some parasites such as Trypanosoma brucei (the causative agent of human African trypanosomiasis, also known as sleeping sickness), this is achieved by expression of a single antigen and periodic switching of the expressed gene, a mechanism called antigenic variation1. Each trypanosome cell in the bloodstream of the mammalian host is coated by ~107 molecules of a single variant surface glycoprotein (VSG). T. brucei has ~2,500 VSG isoforms but a VSG gene can only be transcribed when located in one of 15 telomeric regions termed VSG expression sites. Although it is known that VSG is transcribed by RNA polymerase I in a specific nuclear structure termed the expression site body2, the molecular mechanism that ensures highly selective VSG expression in this sub-nuclear compartment remains largely unknown. In an exciting recent study3, Faria, Luzak and colleagues revealed a specific inter-chromosomal interaction between an active VSG transcription site and a major mRNA splicing locus called the SL-RNA array.

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References

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  1. Department of Biochemistry, University of Oxford, Oxford, UK

    Patryk Ludzia & Bungo Akiyoshi

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  1. Patryk Ludzia
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  2. Bungo Akiyoshi
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Correspondence to Patryk Ludzia or Bungo Akiyoshi.

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Ludzia, P., Akiyoshi, B. Illuminating the mechanism of monogenic antigen expression in trypanosomes. Nat Rev Microbiol 19, 746 (2021). https://doi.org/10.1038/s41579-021-00641-5

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  • DOI: https://doi.org/10.1038/s41579-021-00641-5

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