A newly identified class of RNA molecules has been discovered in bacteria living inside the human body. These circular genetic structures, termed obelisks, differ from known viruses and bacteria and may represent a previously unclassified category of replicating RNA.

The findings emerged from a comprehensive analysis of genetic material drawn from human-associated microbial communities.** Obelisks** appear frequently in samples collected from the mouth and gut, among other locations, and may be present across global populations. Their exact function is still unclear.

What sets these RNA entities apart is their simplicity. They do not encode proteins, nor do they appear to form protective protein shells. Instead, they consist of short loops of RNA that replicate in ways that remain poorly understood.

Thousands of novel RNA loops identified in human microbiomes

Researchers identified more than **3,000 unique types of obelisks **while analysing public metagenomic datasets. These included genetic sequences obtained from human oral and intestinal microbiomes, using high-throughput computational tools designed to detect circular RNA structures within large genomic libraries.

The findings were led by Nobel laureate Andrew Fire of Stanford University and published as a preprint on bioRxiv, a recognised open-access platform for preliminary biological research. The researchers detected closed-loop RNA structures that lack protein-coding regions, distinguishing them from conventionalviral genomes. Instead, the molecules resemble viroids, which are non-coding, circular RNAs known to infect plants, although obelisks have been found only in bacteria associated with humans.

The study used cerebral organoids derived from two human iPSC lines to model the effects of glucocorticoids (GCs). Six treatment conditions were tested in duplicate across four replicates each. Organoids were exposed to either a 10-day chronic GC treatment (100 nM dexamethasone) or a vehicle control (DMSO) starting on day 60, with samples collected at day 70. These day 70 conditions were then cultured for 20 additional days without treatment to generate four day 90 conditions: with or without a 12-hour acute GC exposure. Single-cell RNA-seq and ATAC-seq were performed to examine transcription factor activity and lineage trajectory changes following treatment. Credit: bioRxiv

By applying rigorous sequence filtering to eliminate artefacts, the team identified conserved genetic motifs across multiple samples. Many of the RNA loops were embedded in bacterial genomes, suggesting the structures replicate within microbial cells and may have adapted to specific bacterial hosts over time.

No immediate health effects have been linked to these entities. However, their residence in bacteria that support digestion, immunity and other functions means future research may explore possible indirect roles in human biology.

Atypical structure challenges microbial classification

Obelisks do not conform to known definitions of viruses, plasmids, or other mobile genetic elements. They are protein-free, RNA-only replicators that fall outside established microbial categories. This has drawn interest from researchers studying the boundaries of life and how its simplest forms might operate.

The implications of the discovery extend into evolutionary biology, particularly in ongoing discussions about the origins of RNA-based life. Some theories suggest early life forms may have relied solely on self-replicating RNA. Entities like obelisks, which lack both cellular structure and protein machinery, could offer insight into these early evolutionary stages.

The obelisks exhibit genetic diversity, with different variants appearing in specific regions of the body. This may reflect host-specific adaptations to distinct bacterial communities. Whether they have any regulatory or ecological function in the microbiome remains unknown.

A detailed discussion of this classification issue is presented in the Royal Society Open Science journal, which reviewed recent findings related to novel replicating RNA structures in microbial ecosystems.

Implications for RNA biology and microbial ecology

The discovery aligns with the broader scientific interest in non-coding and circular RNAs, which have been found to play roles in gene regulation and cellular function in both animals and plants. Obelisks are distinct in that they appear to operate independently, without participating in protein synthesis or cellular regulation as currently understood.

The finding also illustrates the power of modern metagenomic sequencing to detect molecular entities that do not fit into established classifications. Advances in bioinformatics have made it possible to examine billions of genetic fragments across microbial ecosystems, revealing forms of life that were previously invisible to researchers.

Additional profiles of researchers involved in the study, such as Dr Mark Peifer at the University of North Carolina and Dr Matthew Sullivan at Ohio State University, reflect the cross-disciplinary approach to understanding these genetic elements. Their work contributes to ongoing investigations into host-microbe interactions, microbial genetics, and minimal RNA replicators.

As more human and environmental microbiomes are sequenced, scientists expect further discoveries of novel RNA forms with unknown roles. Whether obelisks are ancient relics of RNA evolution or modern molecular parasites remains unanswered. Current research efforts aim to determine how they persist, how they are transmitted between bacterial hosts, and whether they interact with other components of microbial communities.