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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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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Ivana Grabundzija & Simon A. Messing & Jainy Thomas & Rachel L. Cosby & Ilija Bilic & Csaba Miskey & Andreas Gogol-Döring & Vladimir Kapitonov & Tanja Diem & Anna Dalda & Jerzy Jurka & Ellen J. Pritha, 2016. "A Helitron transposon reconstructed from bats reveals a novel mechanism of genome shuffling in eukaryotes," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    3. Sachin S. Katti & Inna V. Krieger & Jihyae Ann & Jeewoo Lee & James C. Sacchettini & Tatyana I. Igumenova, 2022. "Structural anatomy of Protein Kinase C C1 domain interactions with diacylglycerol and other agonists," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Tristan Bepler & Kotaro Kelley & Alex J. Noble & Bonnie Berger, 2020. "Topaz-Denoise: general deep denoising models for cryoEM and cryoET," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    5. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    6. Laurie Lannes & Christopher M. Furman & Alison B. Hickman & Fred Dyda, 2023. "Zinc-finger BED domains drive the formation of the active Hermes transpososome by asymmetric DNA binding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Sherwin P. Montaño & Ying Z. Pigli & Phoebe A. Rice, 2012. "The Mu transpososome structure sheds light on DDE recombinase evolution," Nature, Nature, vol. 491(7424), pages 413-417, November.
    8. Philippe Cloutier & Christian Poitras & Mathieu Durand & Omid Hekmat & Émilie Fiola-Masson & Annie Bouchard & Denis Faubert & Benoit Chabot & Benoit Coulombe, 2017. "R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    9. Qiujia Chen & Wentian Luo & Ruth Ann Veach & Alison B. Hickman & Matthew H. Wilson & Fred Dyda, 2020. "Structural basis of seamless excision and specific targeting by piggyBac transposase," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
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