What is already known
Tiny RNA agents known as viroids, which are found in plants, depend on the host cell’s machinery for replication, making them some of the simplest genomes identified. Recent studies have uncovered many new viroid-like RNAs, suggesting that these agents may exist beyond the plant kingdom.
What this research adds
Researchers identified a new class of RNA agents called “obelisks,” found in the human oral and gut microbiotas. These RNA molecules have unique protein-coding regions and appeared in about 10% of 472 human donors, being detected in 7% of stool samples and 50% of oral samples. The analysis revealed about 38,000 distinct obelisk sequences in diverse environments and identified Streptococcus sanguinis as a host for a specific obelisk.
Conclusions
The findings suggest that obelisks are a group of RNA molecules that have colonized the human microbiotas, yet their effects on health and biology remain unknown.
Scientists know a great deal about the bacteria that make up the human microbiota, but much less is understood about viruses and virus-like agents. Now, researchers have identified a new class of virus-like agents known as “obelisks” in oral and stool samples from hundred of people.
The findings, published in Cell, suggest that obelisks are a group of RNA agents that have colonized the human microbiotas, yet their effects on health and biology remain unknown.
Tiny RNA agents known as viroids, which are found in plants, depend on the host cell’s machinery for replication, making them some of the simplest genomes identified. This simplicity has hindered their discovery, but recent studies have uncovered numerous new viroid-like RNAs, indicating that these agents may exist beyond the plant kingdom.
To identify viroid-like RNAs in the human microbiotas, including humans, Ivan Zheludev at Stanford University in California and his colleagues developed a bioinformatics tool called the Viroid Nominator and used it to analyze oral and stool samples from 472 human donors.
Virus-like elements
The analysis uncovered a new type of viroid-like agents called “obelisks.” Obelisks are circular RNA molecules about 1,000 nucleotides long that code for unique proteins.
These RNAs appeared in about 10% of study participants, showing a tendency to inhabit specific body areas. Obelisks were detected in 7% of stool samples and 50% of oral samples.
In stool samples, the researchers identified a type of obelisk called obelisk-α, whose genomic characteristics set it apart from known viroids. Obelisk-α could persist in people over time, suggesting that they are a new type of viroid-like RNA element.
Mysterious functions
After the initial discovery of obelisk-α, the team uncovered 38,500 obelisk-like RNA elements worldwide, all sharing specific proteins, including Oblin-1 and Oblin-2. Oblin-1 likely forms a multi-helical bundle, which could play a role in binding negatively charged molecules such as DNA, while oblin-2 is predicted to form a stable helical structure, which may allow it to interact with itself or similar proteins.
The analysis also revealed that Streptococcus sanguinis is the host of one specific obelisk, called obelisk-S.s. This finding suggests that S. sanguinis can serve as a model for further studies on obelisks, the researchers say.
Indeed, more work is needed to explore obelisks’ biology, their roles in health and disease, and the mechanisms of their interactions with host organisms, the authors add. “Our observations identify obelisks as a class of diverse RNAs of yet-to-be determined impact that have colonized and gone unnoticed in human and global microbiomes.”
