January 21, 2024 | Ivan N. Zheludev, Robert C. Edgar, Maria Jose Lopez-Galiano, Marcos de la Peña, Artem Babaian, Ami S. Bhatt, Andrew Z. Fire
This preprint describes the discovery of a previously unrecognized class of viroid-like elements, termed "Obelisks," identified in human gut metatranscriptomic data. Obelisks are characterized by their circular RNA genome assemblies (~1 kb), predicted rod-like secondary structures, and open reading frames (ORFs) coding for a novel protein superfamily called "Oblins." These elements form a distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Obelisks are prevalent in tested human microbiome metatranscriptomes, with representatives detected in ~7% of stool metatranscriptomes and ~50% of oral metatranscriptomes. Obelisks appear to differ between anatomical sites and can persist in individuals for over 300 days. Large-scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples found across all seven continents and diverse ecological niches. Some Obelisks code for variants of the hammerhead type-III self-cleaving ribozyme. A bacterial species, Streptococcus sanguinis, was found to harbor a specific Obelisk RNA population. Obelisks represent a class of diverse RNAs that have colonized and gone unnoticed in human and global microbiomes.
Obelisks are distinct from viroids and HDV-like elements, as they lack sequence or structural homology to these agents. Structural predictions suggest that Oblin-1 proteins have a novel globular domain, while Oblin-2 may form a leucine zipper alpha helix. Some Obelisks contain ribozyme signatures indicative of a viroid-like replication mechanism. A phylogeny of Oblin-1's domain-A provides evidence for in-family evolution and places ribozyme-bearing Obelisks in distinct clades. Obelisks are globally distributed and are constituents of the human oral and gut microbiomes, occurring in ~10% of human donors in five assayed studies. Obelisks appear to be prevalent in the oral microbiome, with over half of donors positive for such elements. Obelisks are distinct from other sub-viral agents and may represent a new class of RNA elements. The study highlights the need for further research into the biology, evolution, and potential impact of Obelisks on human health.This preprint describes the discovery of a previously unrecognized class of viroid-like elements, termed "Obelisks," identified in human gut metatranscriptomic data. Obelisks are characterized by their circular RNA genome assemblies (~1 kb), predicted rod-like secondary structures, and open reading frames (ORFs) coding for a novel protein superfamily called "Oblins." These elements form a distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Obelisks are prevalent in tested human microbiome metatranscriptomes, with representatives detected in ~7% of stool metatranscriptomes and ~50% of oral metatranscriptomes. Obelisks appear to differ between anatomical sites and can persist in individuals for over 300 days. Large-scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples found across all seven continents and diverse ecological niches. Some Obelisks code for variants of the hammerhead type-III self-cleaving ribozyme. A bacterial species, Streptococcus sanguinis, was found to harbor a specific Obelisk RNA population. Obelisks represent a class of diverse RNAs that have colonized and gone unnoticed in human and global microbiomes.
Obelisks are distinct from viroids and HDV-like elements, as they lack sequence or structural homology to these agents. Structural predictions suggest that Oblin-1 proteins have a novel globular domain, while Oblin-2 may form a leucine zipper alpha helix. Some Obelisks contain ribozyme signatures indicative of a viroid-like replication mechanism. A phylogeny of Oblin-1's domain-A provides evidence for in-family evolution and places ribozyme-bearing Obelisks in distinct clades. Obelisks are globally distributed and are constituents of the human oral and gut microbiomes, occurring in ~10% of human donors in five assayed studies. Obelisks appear to be prevalent in the oral microbiome, with over half of donors positive for such elements. Obelisks are distinct from other sub-viral agents and may represent a new class of RNA elements. The study highlights the need for further research into the biology, evolution, and potential impact of Obelisks on human health.