IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59347-4.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59347-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59347-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Augustine Kong & Michael L. Frigge & Gisli Masson & Soren Besenbacher & Patrick Sulem & Gisli Magnusson & Sigurjon A. Gudjonsson & Asgeir Sigurdsson & Aslaug Jonasdottir & Adalbjorg Jonasdottir & Wend, 2012. "Rate of de novo mutations and the importance of father’s age to disease risk," Nature, Nature, vol. 488(7412), pages 471-475, August.
    2. Oliver Weichenrieder & Klemens Wild & Katharina Strub & Stephen Cusack, 2000. "Structure and assembly of the Alu domain of the mammalian signal recognition particle," Nature, Nature, vol. 408(6809), pages 167-173, November.
    3. Martin Kircher & Chenling Xiong & Beth Martin & Max Schubach & Fumitaka Inoue & Robert J. A. Bell & Joseph F. Costello & Jay Shendure & Nadav Ahituv, 2019. "Saturation mutagenesis of twenty disease-associated regulatory elements at single base-pair resolution," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Fiona A. Hagenbeek & Jana S. Hirzinger & Sophie Breunig & Susanne Bruins & Dmitry V. Kuznetsov & Kirsten Schut & Veronika V. Odintsova & Dorret I. Boomsma, 2023. "Maximizing the value of twin studies in health and behaviour," Nature Human Behaviour, Nature, vol. 7(6), pages 849-860, June.
    2. Samuel S. Kim & Buu Truong & Karthik Jagadeesh & Kushal K. Dey & Amber Z. Shen & Soumya Raychaudhuri & Manolis Kellis & Alkes L. Price, 2024. "Leveraging single-cell ATAC-seq and RNA-seq to identify disease-critical fetal and adult brain cell types," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. repec:plo:pgen00:1006581 is not listed on IDEAS
    4. Jörn Bethune & April Kleppe & Søren Besenbacher, 2022. "A method to build extended sequence context models of point mutations and indels," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Anat Kreimer & Tal Ashuach & Fumitaka Inoue & Alex Khodaverdian & Chengyu Deng & Nir Yosef & Nadav Ahituv, 2022. "Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Kitty Sherwood & Joseph C. Ward & Ignacio Soriano & Lynn Martin & Archie Campbell & Raheleh Rahbari & Ioannis Kafetzopoulos & Duncan Sproul & Andrew Green & Julian R. Sampson & Alan Donaldson & Kai-Re, 2023. "Germline de novo mutations in families with Mendelian cancer syndromes caused by defects in DNA repair," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    7. Richard Culliford & Samuel E. D. Lawrence & Charlie Mills & Zayd Tippu & Daniel Chubb & Alex J. Cornish & Lisa Browning & Ben Kinnersley & Robert Bentham & Amit Sud & Husayn Pallikonda & Anna Frangou , 2024. "Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Tetsushi Sadakata & Yo Shinoda & Akira Sato & Hirotoshi Iguchi & Chiaki Ishii & Makoto Matsuo & Ryosuke Yamaga & Teiichi Furuichi, 2013. "Mouse Models of Mutations and Variations in Autism Spectrum Disorder-Associated Genes: Mice Expressing Caps2/Cadps2 Copy Number and Alternative Splicing Variants," IJERPH, MDPI, vol. 10(12), pages 1-19, November.
    9. Anouk E. J. Janssen & Rebekka M. Koeck & Rick Essers & Ping Cao & Wanwisa Dijk & Marion Drüsedau & Jeroen Meekels & Burcu Yaldiz & Maartje Vorst & Bart Koning & Debby M. E. I. Hellebrekers & Servi J. , 2024. "Clinical-grade whole genome sequencing-based haplarithmisis enables all forms of preimplantation genetic testing," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. Jin Woo Oh & Michael A. Beer, 2024. "Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Kashi Raj Bhattarai & Robert J. Mobley & Kelly R. Barnett & Daniel C. Ferguson & Baranda S. Hansen & Jonathan D. Diedrich & Brennan P. Bergeron & Satoshi Yoshimura & Wenjian Yang & Kristine R. Crews &, 2024. "Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Jonathan E. Shoag & Amoolya Srinivasa & Caitlin A. Loh & Mei Hong Liu & Emilie Lassen & Shana Melanaphy & Benjamin M. Costa & Marta Grońska-Pęski & Nisrine T. Jabara & Shany Picciotto & Una Choi & Any, 2025. "Direct measurement of the male germline mutation rate in individuals using sequential sperm samples," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    13. Michael Kosicki & Dianne Laboy Cintrón & Pia Keukeleire & Max Schubach & Nicholas F. Page & Ilias Georgakopoulos-Soares & Jennifer A. Akiyama & Ingrid Plajzer-Frick & Catherine S. Novak & Momoe Kato &, 2025. "Massively parallel reporter assays and mouse transgenic assays provide correlated and complementary information about neuronal enhancer activity," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    14. Wafeeq Abdelaziz, Asmaa & Ibrahim Abdelmageed, Reham, 2021. "An overview of non-genetic intellectual disability among Egyptian children and adolescents," Children and Youth Services Review, Elsevier, vol. 127(C).
    15. Marie Bernkopf & Ummi B. Abdullah & Stephen J. Bush & Katherine A. Wood & Sahar Ghaffari & Eleni Giannoulatou & Nils Koelling & Geoffrey J. Maher & Loïc M. Thibaut & Jonathan Williams & Edward M. Blai, 2023. "Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    16. Hilary Cope & Edward R Ivimey-Cook & Jacob Moorad, 2022. "Triparental ageing in a laboratory population of an insect with maternal care [Male age alone predicts paternity success under sperm competition when effects of age and past mating effort are exper," Behavioral Ecology, International Society for Behavioral Ecology, vol. 33(6), pages 1123-1132.
    17. repec:plo:pgen00:1003521 is not listed on IDEAS
    18. Arthur S. Lee & Lauren J. Ayers & Michael Kosicki & Wai-Man Chan & Lydia N. Fozo & Brandon M. Pratt & Thomas E. Collins & Boxun Zhao & Matthew F. Rose & Alba Sanchis-Juan & Jack M. Fu & Isaac Wong & X, 2024. "A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    19. repec:plo:pgen00:1003905 is not listed on IDEAS
    20. Stephanie M. Bilinovich & Kristy Lewis & Barbara L. Thompson & Jeremy W. Prokop & Daniel B. Campbell, 2020. "Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics," IJERPH, MDPI, vol. 17(20), pages 1-13, October.
    21. Dang Ton Nguyen & Hai Ha Nguyen & Thuy Duong Nguyen & Thi Thanh Hoa Nguyen & Kaoru Nakano & Kazuhiro Maejima & Aya Sasaki-Oku & Van Ba Nguyen & Duy Bac Nguyen & Bach Quang Le & Jing Hao Wong & Tatsuhi, 2018. "Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability," IJERPH, MDPI, vol. 15(12), pages 1-11, November.
    22. Chunfeng Yun & Zhenjie Wang & Ping He & Chao Guo & Gong Chen & Xiaoying Zheng, 2016. "Prevalence and Parental Risk Factors for Speech Disability Associated with Cleft Palate in Chinese Children—A National Survey," IJERPH, MDPI, vol. 13(11), pages 1-8, November.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59347-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.