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CapTEs enables locus-specific dissection of transcriptional outputs from reference and nonreference transposable elements

ABSTRACT: Transposable elements (TEs) serve as both insertional mutagens and regulatory elements in cells, and their aberrant activity is increasingly being revealed to contribute to diseases and cancers. However, measuring the transcriptional consequences of nonreference and young TEs at individual loci remains challenging with current methods, primarily due to technical limitations, including short read lengths generated and insufficient coverage in target regions. Here, we introduce a long-read targeted RNA sequencing method, Cas9-assisted profiling TE expression sequencing (capTEs), for quantitative analysis of transcriptional outputs for individual TEs, including transcribed nonreference insertions, noncanonical transcripts from various transcription patterns and their correlations with expression changes in related genes. This method selectively identified TE-containing transcripts and outputted data with up to 90% TE reads, maintaining a comparable data yield to whole-transcriptome sequencing. We applied capTEs to human cancer cells and found that internal and inserted Alu elements may employ distinct regulatory mechanisms to upregulate gene expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205935 | GEO | 2023/08/31

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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CapTEs enables locus-specific dissection of transcriptional outputs from reference and nonreference transposable elements

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