法国巴黎文理研究大学Sebastian Amigorena研究团队发现，转座子外显子化产生一个不断演化且具有功能的蛋白质亚型库。2024年12月11日，国际知名学术期刊《细胞》在线发表了这一成果。
研究人员利用转录组组装、核糖体分析和蛋白质组学描述了由mRNA剪接生成的、在人的种群中反复出现的1227种未注释的转座子（TE）外显子化亚型。尽管这些亚型较短且表达水平较低，但它们在个体间共享且能高效翻译。功能分析表明，这些亚型具有稳定的表达、特定的细胞定位，并且在某些情况下具有修改后的功能。
外显子化的TE富含古老基因，而涉及的剪接位点较为近期，且具有演化保守性。此外，外显子化的TE有助于新亚型的二级结构，支持其功能相关性。研究人员认为，TE剪接亚型代表了一个功能蛋白质的多样性库，天然选择可以在其上作用。
据了解，可变剪接通过不同的方式增强蛋白质多样性，其中之一是TE的外显子化。近期的转录组分析发现了成千上万个未注释的剪接转录本，其中包含外显子化的TE，但它们对蛋白质组的贡献及生物学意义仍不明确。
附：英文原文
Title: Transposable element exonization generates a reservoir of evolving and functional protein isoforms
Author: 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, Antonela Merlotti, Sebastian Amigorena
Issue&Volume: 2024-12-11
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.
DOI: 10.1016/j.cell.2024.11.011
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01328-X