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Activity of the mammalian DNA transposon piggyBat from Myotis lucifugus is restricted by its own transposon ends

Author

Listed:
  • Alison B. Hickman

    (National Institutes of Health)

  • Laurie Lannes

    (National Institutes of Health
    PSL Research University)

  • Christopher M. Furman

    (National Institutes of Health
    International Flavors and Fragrances)

  • Christina Hong

    (National Institutes of Health)

  • Lidiya Franklin

    (National Institutes of Health)

  • Rodolfo Ghirlando

    (National Institutes of Health)

  • Arpita Ghosh

    (Louisiana State University)

  • Wentian Luo

    (Vanderbilt University Medical Center)

  • Parthena Konstantinidou

    (National Institutes of Health)

  • Hernán A. Lorenzi

    (National Institutes of Health)

  • Anne Grove

    (Louisiana State University)

  • Astrid D. Haase

    (National Institutes of Health)

  • Matthew H. Wilson

    (Vanderbilt University Medical Center
    Department of Veterans Affairs
    Vanderbilt University
    Vanderbilt University)

  • Fred Dyda

    (National Institutes of Health)

Abstract

Members of the piggyBac superfamily of DNA transposons are widely distributed in host genomes ranging from insects to mammals. The human genome has retained five piggyBac-derived genes as domesticated elements although they are no longer mobile. Here, we have investigated the transposition properties of piggyBat from Myotis lucifugus, the only known active mammalian DNA transposon, and show that its low activity in human cells is due to subterminal inhibitory DNA sequences. Activity can be dramatically improved by their removal, suggesting the existence of a mechanism for the suppression of transposon activity. The cryo-electron microscopy structure of the piggyBat transposase pre-synaptic complex showed an unexpected mode of DNA binding and recognition using C-terminal domains that are topologically different from those of the piggyBac transposase. Here we show that structure-based rational re-engineering of the transposase through the removal of putative phosphorylation sites and a changed domain organization - in combination with truncated transposon ends - results in a transposition system that is at least 100-fold more active than wild-type piggyBat.

Suggested Citation

  • Alison B. Hickman & Laurie Lannes & Christopher M. Furman & Christina Hong & Lidiya Franklin & Rodolfo Ghirlando & Arpita Ghosh & Wentian Luo & Parthena Konstantinidou & Hernán A. Lorenzi & Anne Grove, 2025. "Activity of the mammalian DNA transposon piggyBat from Myotis lucifugus is restricted by its own transposon ends," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55784-9
    DOI: 10.1038/s41467-024-55784-9
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