Massively parallel jumping assay decodes Alu retrotransposition activity
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 affe...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59347-4 |
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| _version_ | 1849729036470714368 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Navneet Matharu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-29b7ea43f3bd408cbbdf406e5e78e3e2 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-29b7ea43f3bd408cbbdf406e5e78e3e22025-08-20T03:09:20ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-59347-4Massively parallel jumping assay decodes Alu retrotransposition activityNavneet Matharu0Jingjing Zhao1Ajuni Sohota2Linbei Deng3Yan Hung4Zizheng Li5Kelly An6Jasmine Sims7Sawitree Rattanasopha8Thomas J. Meyer9Lucia Carbone10Martin Kircher11Nadav Ahituv12Department of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoDivision of Genetics, Oregon National Primate Research CenterDivision of Genetics, Oregon National Primate Research CenterBerlin Institute of Health of Health at Charité—Universitätsmedizin BerlinDepartment of Bioengineering and Therapeutic Sciences, University of California San FranciscoAbstract 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.https://doi.org/10.1038/s41467-025-59347-4 |
| spellingShingle | 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 Massively parallel jumping assay decodes Alu retrotransposition activity Nature Communications |
| title | Massively parallel jumping assay decodes Alu retrotransposition activity |
| title_full | Massively parallel jumping assay decodes Alu retrotransposition activity |
| title_fullStr | Massively parallel jumping assay decodes Alu retrotransposition activity |
| title_full_unstemmed | Massively parallel jumping assay decodes Alu retrotransposition activity |
| title_short | Massively parallel jumping assay decodes Alu retrotransposition activity |
| title_sort | massively parallel jumping assay decodes alu retrotransposition activity |
| url | https://doi.org/10.1038/s41467-025-59347-4 |
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