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Viroid-like colonists of human microbiomes

Affiliations
  • 1Stanford University, Department of Biochemistry, Stanford, CA, USA. Electronic address: zheludev@stanford.edu.
  • 2Independent researcher, Corte Madera, CA, USA.
  • 3Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia-CSIC, Valencia, Spain.
  • 4University of Toronto, Department of Molecular Genetics, Toronto, ON, Canada; University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON, Canada.
  • 5Stanford University, Department of Genetics, Stanford, CA, USA; Stanford University, Department of Medicine, Division of Hematology, Stanford, CA, USA.
  • 6Stanford University, Department of Genetics, Stanford, CA, USA; Stanford University, Department of Pathology, Stanford, CA, USA. Electronic address: afire@stanford.edu.

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October 31, 2024

Abstract

Here, we describe “obelisks,” a class of heritable RNA elements sharing several properties: (1) apparently circular RNA ∼1 kb genome assemblies, (2) predicted rod-like genome-wide secondary structures, and (3) open reading frames encoding a novel “Oblin” protein superfamily. A subset of obelisks includes a variant hammerhead self-cleaving ribozyme. Obelisks form their own phylogenetic group without detectable similarity to known biological agents. Surveying globally, we identified 29,959 distinct obelisks (clustered at 90% sequence identity) from diverse ecological niches. Obelisks are prevalent in human microbiomes, with detection in ∼7% (29/440) and ∼50% (17/32) of queried stool and oral metatranscriptomes, respectively. We establish Streptococcus sanguinis as a cellular host of a specific obelisk and find that this obelisk’s maintenance is not essential for bacterial growth. 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.

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