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Cartography and mechanism of enhanced transcriptome plasticity by transposable elements

ABSTRACT: Transposable elements (TEs) in our genome are the heritage of ancient parasitic infections. While most of human DNA is comprised of TEs and TE-derived elements, their repetitive nature poses technical challenges and thus little is known about their positional identity and regulatory roles. Here, by integrating long-read and multidimensional transcriptional analyses, we investigated when, where and how TEs become part of a gene. We characterized how TE-derived isoform and new genes change across mouse-human variation and are linked to gene regulatory networks controlling cell states during differentiation, organogenesis and health (aging and pathological states). Mechanistically, we identified an RNA degradation-dependent and a splicing-dependent quality control mechanism that operate independently of conventional mechanisms of TE suppression (DNA methylation and heterochromatinization) and prevents TE-exonization and TE-induced cell differentiation. Overall, our findings reveal new mechanisms by which viral-derived elements enhance transcriptome plasticity.

ORGANISM(S): Mus musculus

PROVIDER: GSE297796 | GEO | 2026/01/06

REPOSITORIES: GEO

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Project description:Background: Transposable elements (TEs) represent a substantial fraction of the genomes, playing a major role in evolution, as sources of genetic variability. To fully appraise the role of TE in the acquisition of genetic novelty in genome evolution, we must also consider the impact of their own transcriptional activity. Results: We studied impact of TE transcriptional activity on gene using high-throughput RNA-Seq sequencing in Drosophila melanogaster. TEs, which turn out to be expressed in euchromatin as well as in heterochromatin, interact with genes at different levels. The observed transcription from TEs involve canonical or non-canonical transcription start sites (TSSs) distributed along their sequence. We also find evidences for potential bidirectional transcription from the TE promoter regions where the antisense transcript is co-opted by the host genome as TSSs of a gene. We found that active TEs seem to accumulate in the 5' upstream regions of the genes, and possibly provide an alternative transcript of the nearby gene. Indeed, predominantly, the TE transcript is collinear and overlapping the gene. Apart from the 5' upstream regions, we also found that most active TEs are transcribed on the gene transcript strand. Conversely, few transcripts from TE are anti sense with respect to the gene. This suggests that they have a disruptive action and are counter-selected. The only exceptions are for TEs located into introns, where they could provide another complex way of gene regulation, and in the 3' downstream region, where other mechanisms akin to siRNAs could take place. Finally, we noted several cases where the cryptic TSS is located on TE fragments corresponding to a low complexity sequence. Frequently these TE fragments appear to be over-represented when close to genes, suggesting a possible selected role. Conclusion: Altogether, these results suggest that active transposable elements influence host gene transcription. It is likely that some features of transposable elements have been exaptated in order to enrich the genes repertoire by opening routes to sub- or neo-functionalization. Examination of the transcription produced by transposable elements in D. melanogaster

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Cartography and mechanism of enhanced transcriptome plasticity by transposable elements

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