Transposable element–gene chimera cartography, origination and role in enhancing transcriptome plasticity
Transposable elements (TEs) in the human genome are the heritage of ancient parasitic infections. While most of human DNA comprises TEs and TE-derived elements, their repetitive nature poses technical challenges; thus, little is known about their positional identity and regulatory roles. Here, by integrating long-read and multidimensional transcriptional analyses, we investigate when, where and how TEs become part of a gene. We characterize how TE-derived isoforms change across mouse-human variation and how they are linked to gene regulatory networks controlling cell states during differentiation, organogenesis and health (aging and pathological states). Mechanistically, we identify an RNA degradation-dependent and splicing-dependent quality control mechanism that operates independently of conventional mechanisms of TE suppression, such as DNA methylation and heterochromatinization, and prevents TE-chimera expression and TE-induced cell differentiation. Overall, our findings unveil mechanisms by which viral-derived elements enhance transcriptome plasticity.
Authors
- Evgeny Z. Kvon (ORCID: https://orcid.org/0000-0002-1562-0945)
- Minji Byun (ORCID: https://orcid.org/0000-0002-2830-4079)
- Jessica Ho (ORCID: https://orcid.org/0000-0003-2234-2602)
- Denis Torre (ORCID: https://orcid.org/0000-0003-4615-223X)
- Youngseo Cheon
- Mingqi Zhou (ORCID: https://orcid.org/0000-0002-4605-5467)
- Marcus Seldin (ORCID: https://orcid.org/0000-0001-8026-4759)
- Ivan Marazzi (ORCID: https://orcid.org/0000-0003-3376-0922)
- Ernesto Guccione (ORCID: https://orcid.org/0000-0001-7764-5307)
- Yesai Fstkchyan (ORCID: https://orcid.org/0000-0001-9950-2841)
- Yoseop Yoon (ORCID: https://orcid.org/0000-0002-6062-0979)
- Yongsheng Shi
- Kwangbeom Hyun
- Fairlie Reese
- Liang Liu
- Daniel Tu Quach
- Frederick J. Arnold
- Enza Maria Valente
- Lauren Faraone
- Uttiya Basu
- Yingcong Li
- Erik Glen Alvstad
- Jennifer Nguyen
- Tianxiong Yu
Institutions
- Cedars-Sinai Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Massachusetts Chan Medical School (US)
- University of California, Irvine (US)
- Washington University in St. Louis (US)
- University of Pavia (IT)
- Columbia University Irving Medical Center (US)
- Barcelona Supercomputing Center (ES)
- Duke-NUS Medical School (SG)
- Universitat Politècnica de Catalunya (ES)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Structural & Molecular Biology
- Published
- 2026-02-25
- DOI
- https://doi.org/10.1038/s41594-026-01757-z
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 0.00