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Massively parallel jumping assay decodes Alu retrotransposition activity

Author

Listed:
  • Navneet Matharu

    (University of California San Francisco
    University of California San Francisco)

  • Jingjing Zhao

    (University of California San Francisco
    University of California San Francisco)

  • Ajuni Sohota

    (University of California San Francisco
    University of California San Francisco)

  • Linbei Deng

    (University of California San Francisco
    University of California San Francisco)

  • Yan Hung

    (University of California San Francisco
    University of California San Francisco)

  • Zizheng Li

    (University of California San Francisco)

  • Kelly An

    (University of California San Francisco
    University of California San Francisco)

  • Jasmine Sims

    (University of California San Francisco
    University of California San Francisco)

  • Sawitree Rattanasopha

    (University of California San Francisco
    University of California San Francisco)

  • Thomas J. Meyer

    (Oregon National Primate Research Center
    Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc.)

  • Lucia Carbone

    (Oregon National Primate Research Center
    Oregon Health and Science University
    Oregon Health and Science University
    Oregon Health and Science University)

  • Martin Kircher

    (Berlin Institute of Health of Health at Charité—Universitätsmedizin Berlin
    University of Lübeck)

  • Nadav Ahituv

    (University of California San Francisco
    University of California San Francisco)

Abstract

The human genome contains millions of copies of retrotransposons that are silenced but many of these copies have potential to become active if mutated, having phenotypic consequences, including disease. However, it is not thoroughly understood how nucleotide changes in retrotransposons affect their jumping activity. Here, we develop a massively parallel jumping assay (MPJA) that tests the jumping potential of thousands of transposons en masse. We generate a nucleotide variant library of four Alu retrotransposons containing 165,087 different haplotypes and test them for their jumping ability using MPJA. We found 66,821 unique jumping haplotypes, allowing us to pinpoint domains and variants vital for transposition. Mapping these variants to the Alu-RNA secondary structure revealed stem-loop features that contribute to jumping potential. Combined, our work provides a high-throughput assay that assesses the ability of retrotransposons to jump and identifies nucleotide changes that have the potential to reactivate them in the human genome.

Suggested Citation

  • Navneet Matharu & Jingjing Zhao & Ajuni Sohota & Linbei Deng & Yan Hung & Zizheng Li & Kelly An & Jasmine Sims & Sawitree Rattanasopha & Thomas J. Meyer & Lucia Carbone & Martin Kircher & Nadav Ahituv, 2025. "Massively parallel jumping assay decodes Alu retrotransposition activity," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59347-4
    DOI: 10.1038/s41467-025-59347-4
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