Transposable element exonization generates a reservoir of evolving and functional protein isoforms
Alternative splicing enhances protein diversity in different ways, including through exonization of transposable elements (TEs). Recent transcriptomic analyses identified thousands of unannotated spliced transcripts with exonizing TEs, but their contribution to the proteome and biological relevance remains unclear. Here, we use transcriptome assembly, ribosome profiling, and proteomics to describe a population of 1,227 unannotated TE exonizing isoforms generated by mRNA splicing and recurrent in human populations. Despite being shorter and lowly expressed, these isoforms are shared between individuals and efficiently translated. Functional analyses show stable expression, specific cellular localization, and, in some cases, modified functions. Exonized TEs are rich in ancient genes, whereas the involved splice sites are recent and can be evolutionarily conserved. In addition, exonized TEs contribute to the secondary structure of the emerging isoforms, supporting their functional relevance. We conclude that TE-spliced isoforms represent a diversity reservoir of functional proteins on which natural selection can act.
Authors
- Julien Diharce (ORCID: https://orcid.org/0000-0002-6400-927X)
- Yago A. Arribas (ORCID: https://orcid.org/0000-0003-4434-3075)
- Joshua J. Waterfall (ORCID: https://orcid.org/0000-0002-3762-5050)
- Pierre‐Emmanuel Bonté (ORCID: https://orcid.org/0000-0002-9732-5826)
- Sebastián Amigorena (ORCID: https://orcid.org/0000-0001-8583-8416)
- Lluís Quintana‐Murci (ORCID: https://orcid.org/0000-0003-2429-6320)
- Montserrat Carrascal (ORCID: https://orcid.org/0000-0002-0205-2176)
- Maxime Rotival (ORCID: https://orcid.org/0000-0003-2519-8044)
- Antonela Merlotti (ORCID: https://orcid.org/0000-0001-7015-9824)
- Patricia Legoix
- Benjamin Sadacca (ORCID: https://orcid.org/0000-0001-5843-618X)
- Elisa Bonnin (ORCID: https://orcid.org/0009-0005-6544-2736)
- Marianne Burbage (ORCID: https://orcid.org/0000-0003-0686-2608)
- Vanessa Casas
- P. B. Klein
- Christel Goudot (ORCID: https://orcid.org/0000-0001-6037-2314)
- Guadalupe Suárez (ORCID: https://orcid.org/0000-0002-6943-6916)
- Sylvain Baulande (ORCID: https://orcid.org/0000-0003-3104-1684)
- Blandine Baudon (ORCID: https://orcid.org/0000-0001-9536-6459)
- Basma Mchich
- Apollinaire Roubert
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- University of Reunion Island (RE)
- Université Paris Sciences et Lettres (FR)
- Evolutionary Genomics (United States) (US)
- Immunité et Cancer (FR)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- Institut Curie (FR)
Publication Details
- Journal
- Cell
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.cell.2024.11.011
- Citations
- 35
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 20.39
Funders
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Fondation ARC pour la Recherche sur le Cancer