Expression spectrum of TE-driven transcripts in human adult tissues

BACKGROUND: Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored. RESULTS: In this study, we systematically analyze 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-driven transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific gene regulation. We identify sex-specific expression of TE-driven transcripts regulated by sex hormones in breast tissue between females and males. Our results suggest that TE-driven alternative transcription initiation significantly enhances the variety of translated protein products, e.g., changes in the N-terminal peptide length of WNT2B caused by TE-driven transcription result in isoform-specific subcellular localization. Additionally, we identify 68 human-specific TE-driven transcripts of genes, which are involved in distinct biological processes. CONCLUSIONS: These findings indicate the regulatory role of TEs in human genome evolution and highlight their substantial contribution to the diversification of transcriptional and translational outputs.