Telomeric repeat-containing lncRNA TERRA targets non-telomeric DNA in trans via R-loops

Telomeres are transcribed into telomeric repeat-containing RNA (TERRA), a long non-coding RNA (lncRNA) with established roles in telomere maintenance and genome stability. While TERRA's formation of R-loops at telomeric regions is well documented, its potential interactions with non-telomeric DNA remain less clear. Here, through bioinformatic reanalysis of publicly available datasets, we identify evidence that TERRA may also associate with non-telomeric genomic regions in trans via R-loop formation. These interactions are enriched at loci containing tandem telomeric repeat motifs, suggesting a sequence-dependent mode of binding. Integrative analysis further indicates that such distal TERRA-DNA associations could influence the expression of telomere maintenance-related genes, hinting at a possible gene-modulating role. While based on bioinformatics analysis, these findings generate testable hypotheses that warrant experimental validation and open new avenues for exploring how TERRA, and potentially other lncRNAs, contribute to transcriptional regulation and chromatin organization.