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

TY - JOUR

T1 - Telomeric repeat-containing lncRNA TERRA targets non-telomeric DNA in trans via R-loops

AU - Shehata, Saifeldin N.

AU - Mendez, Akram

AU - Mondal, Tanmoy

AU - Vaid, Roshan

N1 - Publisher Copyright: © 2025 The Authors

PY - 2025

Y1 - 2025

N2 - 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.

AB - 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.

KW - Gene Regulation

KW - Non-telomeric DNA binding

KW - R-loop

KW - TERRA lncRNA

UR - https://www.scopus.com/pages/publications/105023838106

U2 - 10.1016/j.csbj.2025.11.063

DO - 10.1016/j.csbj.2025.11.063

M3 - Article

C2 - 41439025

AN - SCOPUS:105023838106

SN - 2001-0370

VL - 27

SP - 5450

EP - 5458

JO - Computational and structural biotechnology journal

JF - Computational and structural biotechnology journal

ER -