RNA:DNA triplexes: a mechanism for epigenetic communication between hosts and microbes?

Abstract

Molecular communication between host and microbe is mediated by the transfer of many differentclasses of macromolecules. Recently, the traffickingof RNA molecules between organisms has gained prominence as an efficientway to manipulate gene expression via RNA interference (RNAi). Here, we posit a new epigenetic control mechanism based on triple helix (triplex) structures comprising nucleic acids from both host and microbe. Indeed, RNA:DNA triplexes are known to regulate gene expression in humans, but it is unknown whether interkingdom triplexes are formed either to manipulate host processes during pathogenesis or as a host defense response. We hypothesize that a fraction of the extracellular RNAs commonly released by microbes (e.g., bacteria, fungi, and protists) and their hosts form triplexes with the genome of the other species, thereby impacting chromatin conformation and gene expression. We invite the fieldto consider interkingdom triplexes as unexplored weaponry in the arms race between host and microbe.