Transposable element exonization generates a reservoir of evolving and functional protein isoforms

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2024-12-11 DOI:10.1016/j.cell.2024.11.011

Yago A. Arribas, Blandine Baudon, Maxime Rotival, Guadalupe Suárez, Pierre-Emmanuel Bonté, Vanessa Casas, Apollinaire Roubert, Paul Klein, Elisa Bonnin, Basma Mchich, Patricia Legoix, Sylvain Baulande, Benjamin Sadacca, Julien Diharce, Joshua J. Waterfall, Catherine Etchebest, Montserrat Carrascal, Christel Goudot, Lluís Quintana-Murci, Marianne Burbage, Sebastian Amigorena

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引用次数: 0

Abstract

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.

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.