Direct DNA-RNA interactions dynamically decorate core functional elements within the human genome

ABSTRACT: Half a century ago the rules that govern DNA-RNA interactions were thoroughly crafted. However, our understanding of the role played by these structures within the cell remains fragmentary. In that regard, early observations suggested that the human genome is decorated with RNA molecules in vivo, and though we cannot ascertain that those interactions are built through direct DNA-RNA contact, a large body of circumstantial evidence supports that DNA-RNA platforms play key roles in genome control. Conceptually, RNA molecules provide an exquisite targeting scaffold to interfere with biological processes or target protein complexes to specific genomic locations. However, due to the lack of a technological leap, only a handful of documented examples describing endogenous DNA-interacting RNAs have been reported. To tackle this issue we developed DNA-interacting RNA – Identification (DiR-ID) and DNA-interacting RNA – Footprint (DiR-F), versatile methods enabling the identification of DNA-interacting RNAs and retrieval of DNA-RNA interaction footprints at single nucleotide resolution and genome-wide scale. Notably, we observed that thousands of DNA-RNA platforms are scattered throughout the genome displaying a large overlap with core functional elements (active/inactive TSS/TTS, enhancers, and promoters, facultative and constitutive heterochromatin among others) suggesting that DNA-interacting RNA molecules play a role in chromatin organization and functionality. Indeed, by interfering with JHDM1D-AS1 non-coding RNA -a bona fide DNA-interacting RNA that binds to specific sites contained within facultative heterochromatin- we altered the local epigenetic landscape, thus indicating that DNA-RNA platforms contribute to the establishment/maintenance of functional chromatin states. Finally, we identified a large number of transcripts engaged into DNA-RNA platforms and demonstrated that their recruitment to DNA respond to biological cues. All in all, we show that coding and non-coding RNAs establish direct interactions with DNA decorating hitherto identified regulatory elements throughout the genome and glimpse at a genome-wide remodeling of the chromatin landscape as a result of the recruitment/dismissal of DNA-interacting RNAs to its specific binding sites.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102093 | GEO | 2026/07/29

REPOSITORIES: GEO