A hidden language between two worlds?

Researchers propose new role of RNA triplexes in communication between microbes and hosts

For a long time, RNA was considered DNA’s “little sister” – less stable, just a messenger substance without its own role in the limelight. But in recent decades, research has shown that RNA is much more: it regulates genes, controls cell processes and may even have played a key role in the origin of life. Now researchers are raising a fascinating question: Could RNA also be another language that microbes use to influence their hosts?

In an article in the scientific journal mBio, Amelia Barber and Holger Bierhoff from the Friedrich Schiller University Jena, together with Matthew Blango from the Leibniz-HKI, have put forward a new hypothesis: Microbes could use so-called RNA:DNA triplexes to influence the genetic processes of their hosts. These special structures may represent a new level of epigenetic communication, a kind of molecular whisper between microbes and their hosts such as humans, plants or animals.

Triplexes: A new dimension of communication?

These RNA:DNA triplexes consist of three strands and form when a single-stranded RNA molecule interacts specifically with the large groove of the double-stranded DNA. Such structures are already known to play a role in gene regulation in humans. The researchers suspect that microbes use their RNA to form such triplexes with the DNA of their hosts and thus alter gene expression. Among other things, this could lead to a change in the immune response and give the microbes an evolutionary advantage.

Microbes as masters of manipulation

Bacteria, fungi and parasites are true masters of manipulation. They have used a wide variety of molecules to influence the biological processes of their hosts to their own advantage for a long time. The research team led by Barber, Bierhoff and Blango suggests that microbes could possibly use “triplexes” of RNA and DNA molecules to influence the genes of their hosts - a mechanism that has hardly been researched to date.

It’s just the beginning

The understanding of such RNA:DNA triplexes from molecules of different species is still in its infancy. “We know that RNA:DNA triplexes can play an important role in regulating the immune response,” explains Matthew Blango. “Now we want to find out whether microbes use these structures to influence their hosts - and whether we can use these findings to develop new therapies against infectious diseases.”

An appeal to the research community

The research team is now inviting the scientific community to tackle this exciting question and examine existing data sets. “The ongoing development of bioinformatics methods offers us the opportunity to explore these fascinating interactions in greater depth,” says Blango. “We hope that our hypothesis will open new doors for the study of molecular communication between microbes and their hosts.”

In their “FuRTHER” project, funded by the Leibniz Association, the specialists in biochemistry (Bierhoff), bioinformatics (Barber, both University of Jena) and microbiology (Blango, Leibniz-HKI) are demonstrating, how interdisciplinary collaboration between several institutions can succeed. Research into the communication of microorganisms thus contributes to the understanding of complex organismic interactions in our environment and is part of the Cluster of Excellence "Balance of the Microverse”.

Original publication

Bierhoff H, Barber AE, Blango MG (2024) RNA:DNA triplexes: a mechanism for epigenetic communication between hosts and microbes? mBio, https://doi.org/10.1128/mbio.01982-24.