New RNA Entities Found in Human Microbiome Challenge Definitions of Viruses
Researchers have identified thousands of protein-free, circular RNA molecules living inside human-associated bacteria, raising new questions for microbiology labs about how life is classified.
Laboratory leaders accustomed to classifying organisms as bacteria, viruses, or parasites may soon need to account for something entirely different. Researchers have identified a previously unknown class of RNA molecules living inside bacteria associated with the human body—entities that replicate but do not fit into any existing biological category.
The structures, called “obelisks,” are circular RNA molecules found primarily in bacteria from the human mouth and gut. They are neither living cells nor conventional viruses. Instead, they exist as short loops of RNA that replicate within microbial hosts through mechanisms that scientists do not yet understand.
Protein-Free RNA Replicators Emerge from Large-Scale Metagenomic Analysis
What makes obelisks particularly unusual is what they lack. According to the researchers, the RNA loops are “protein-free, RNA-only replicators.” They do not encode proteins, nor do they form protective capsids or membranes. This places them outside established definitions of viruses, plasmids, or other mobile genetic elements.
The discovery emerged from a large-scale analysis of publicly available metagenomic data drawn from human-associated microbial communities. Using computational tools designed to identify circular RNA structures, the research team screened vast genomic libraries from oral and intestinal microbiomes.
That effort revealed more than 3,000 distinct obelisk sequences, many of which appeared repeatedly across samples from different individuals and geographic regions. The work was led by Nobel laureate Andrew Fire of Stanford University and published as a preprint on bioRxiv.
To ensure the findings were not artefacts of sequencing or data processing, the team applied stringent filtering criteria. After removing false positives, they identified conserved genetic motifs shared among multiple obelisks. Many of the RNA loops were found embedded within bacterial genomes, suggesting they replicate inside microbial cells and may have adapted to specific bacterial hosts over time.
Unknown Function, Broad Implications for Microbiology and Evolution
Although obelisks resemble plant viroids, non-coding, circular RNAs that infect plants, the researchers note a key difference: obelisks have so far been identified only in bacteria associated with humans. Their biological role remains unknown.
At present, there is no evidence linking obelisks to disease. However, their presence in bacteria that support digestion, immune function, and other critical processes raises questions about whether they may have indirect effects on human health. Researchers also observed that different obelisk variants appear in specific body sites, hinting at localized adaptation within the microbiome.
Beyond immediate clinical relevance, the discovery has broader implications for microbial classification and evolutionary biology. Obelisks do not conform to known categories, challenging long-standing assumptions about what constitutes a replicating biological entity.
Some scientists suggest these RNA structures could inform theories about early life on Earth, when self-replicating RNA may have existed before cells and proteins. As one review in Royal Society Open Science notes, such entities sit at the edge of life as currently defined.
For laboratory leaders, the finding highlights the expanding reach of metagenomic sequencing and bioinformatics. As clinical and research labs generate and analyze ever-larger datasets, they are increasingly likely to encounter biological signals that defy traditional taxonomy.
Whether obelisks prove to be ancient evolutionary relics or modern molecular passengers, their discovery is a reminder that the microbiome—and the lab tools used to study it—still holds fundamental surprises.
—Janette Wider
