Viroid-like colonists of human microbiomes
Open accessPreprint — published as 10.1016/j.cell.2024.09.033 · Paper page
Abstract
Here, we describe the “Obelisks,” a previously unrecognised class of viroid-like elements that we first identified in human gut metatranscriptomic data. “Obelisks” share several properties: (i) apparently circular RNA ∼1kb genome assemblies, (ii) predicted rod-like secondary structures encompassing the entire genome, and (iii) open reading frames coding for a novel protein superfamily, which we call the “Oblins”. We find that Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Further, Obelisks are prevalent in tested human microbiome metatranscriptomes with representatives detected in ∼7% of analysed stool metatranscriptomes (29/440) and in ∼50% of analysed oral metatranscriptomes (17/32). Obelisk compositions appear to differ between the anatomic sites and are capable of persisting in individuals, with continued presence over >300 days observed in one case. Large scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples from all seven continents and in diverse ecological niches. From this search, a subset of Obelisks are identified to code for Obelisk-specific variants of the hammerhead type-III self-cleaving ribozyme. Lastly, we identified one case of a bacterial species ( Streptococcus sanguinis ) in which a subset of defined laboratory strains harboured a specific Obelisk RNA population. As such, Obelisks comprise a class of diverse RNAs that have colonised, and gone unnoticed in, human, and global microbiomes.
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- Authors
- Zheludev, I. N., Edgar, R. C., Lopez-Galiano, M. J., de la Peña, M., Babaian, A., Bhatt, A. S., & Fire, A. Z.
- Affiliations
- Stanford University (US)
- University of Toronto (CA)
- Stanford Medicine (US)
- Corresponding author
- Zheludev, Ivan N.
- Fire, Andrew Z.
- ORCID
- Venue
- Cell
- Publisher
- openRxiv
- Published
- 2024-01-21
- Volume
- 187
- Issue
- 23
- Pages
- 6521-6536.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC11949080
- OpenAlex
- W4403959930
- Cited by
- 73
- References
- 125
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 24
- FWCI
- 19.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RiuNet (Universitat Politècnica de València) (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- PubMed Central (submittedVersion, cc-by-nc)
- Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, cc-by-nc)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01AI148623, R01AI143757)
- American Welding Society
- Allen Institute
- Generalitat Valenciana (PROMETEO CIPROM/2022/21, CIPROM/2022/21)
- Universitat de València
- University of Toronto
- University of British Columbia
- National Institutes of Health
- School of Medicine, Stanford University
- Stand Up To Cancer
- Canadian Institutes of Health Research (PTJ-496709)
- National Institute of General Medical Sciences (R35GM130366)
- National Institute of Allergy and Infectious Diseases (R01AI148623, R01AI143757, 3.1416)
- Topics
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- obelisks, human microbiome, Streptococcus sanguinis, RNA secondary structure, metatranscriptomics, oral microbiota, gut microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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