The discovery and mapping of stable  DNA-RNA hybrid triplexes open up important new perspectives in molecular biology, with potential applications across several fields of research and medicine.

For scientists studying gene regulation, this work introduces a new layer of control mechanisms. The identification of hybrid triplexes in regulatory regions of the genome—such as gene promoters—suggests that these structures could act as molecular switches, either promoting or repressing gene expression. This expands our current understanding of transcriptional control, which has largely focused on protein-based mechanisms, and highlights RNA's emerging structural role in influencing which genes are turned on or off.

Researchers in the field of epigenetics may also find these findings highly valuable. Because triplexes are enriched in specific chromatin environments, there is potential for them to be involved in epigenetic modifications—such as influencing DNA methylation patterns or histone positioning—that contribute to heritable changes in gene activity. Understanding these processes could shed light on how certain gene expression profiles are maintained or altered in different cell types and during development.

In genome architecture research, these triplexes could represent a physical mechanism by which the three-dimensional folding of DNA is regulated. Since the human genome is highly compacted inside the nucleus, structures like hybrid triplexes may help stabilize specific chromatin loops or domains, affecting long-range gene interactions and overall nuclear organization.

Importantly, this research may also have future applications in biomedicine, particularly in diseases linked to misregulated gene expression, such as various forms of cancer, neurodegenerative disorders, and developmental syndromes. Aberrant formation or disruption of these triplexes could interfere with normal gene control, offering both diagnostic insights and potential therapeutic targets. For example, drugs or RNA-based therapies could be designed to stabilize or disrupt specific triplex structures, effectively modulating gene expression without altering the underlying genetic code.

Furthermore, the computational tool developed by the research team to predict triplex formation sites provides a powerful resource for the broader scientific community. It allows researchers to scan entire genomes for potential triplex-forming regions and correlate them with known regulatory elements or disease-associated loci, accelerating hypothesis generation and experimental design.

As Dr. Modesto Orozco, lead investigator and head of the Molecular Modelling and Bioinformatics Lab at IRB Barcelona, summarizes:

Our understanding of how RNA regulates chromatin is evolving. These findings provide compelling evidence that RNA doesn’t just carry genetic messages—it can physically shape and influence the function of DNA through direct interaction. This insight opens up exciting directions in both fundamental biology and therapeutic development.

In essence, this research redefines RNA’s role in the cell—from a passive messenger to an active architectural and regulatory molecule—offering new tools and concepts to unravel the complexity of gene regulation and genome organization.

Source: https://www.pcb.ub.edu/en/a-scientific-team-at-irb-barcelona-reveals-the-role-of-hybrid-dna-rna-triplexes-in-gene-regulation/