Naturally ornate RNA-only complexes revealed by cryo-EM

Rachael C. Kretsch, Yuan Wu, Svetlana A. Shabalina, Hyunbin Lee, Grace Nye, Eugene V. Koonin, Alex Gao, Wah Chiu () and Rhiju Das ()
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Rachael C. Kretsch: Stanford University
Yuan Wu: Stanford University
Svetlana A. Shabalina: National Institutes of Health
Hyunbin Lee: Stanford University School of Medicine
Grace Nye: SSRL–SLAC National Accelerator Laboratory
Eugene V. Koonin: National Institutes of Health
Alex Gao: Stanford University
Wah Chiu: Stanford University
Rhiju Das: Stanford University

Nature, 2025, vol. 643, issue 8073, 1135-1142

Abstract: Abstract The structures of natural RNAs remain poorly characterized and may hold numerous surprises1–4. Here we report three-dimensional structures of three large ornate bacterial RNAs using cryo-electron microscopy (cryo-EM). GOLLD (Giant, Ornate, Lake- and Lactobacillales-Derived), ROOL (Rumen-Originating, Ornate, Large) and OLE (Ornate Large Extremophilic) RNAs form homo-oligomeric complexes whose stoichiometries are retained at lower concentrations than measured in cells. OLE RNA forms a dimeric complex with long co-axial pipes spanning two monomers. Both GOLLD and ROOL form distinct RNA-only multimeric nanocages with diameters larger than the ribosome, each empty except for a disordered loop. Extensive intramolecular and intermolecular A-minor interactions, kissing loops, an unusual A–A helix and other interactions stabilize the three complexes. Sequence covariation analysis of these large RNAs reveals evolutionary conservation of intermolecular interactions, supporting the biological importance of large, ornate RNA quaternary structures that can assemble without any involvement of proteins.

Date: 2025
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DOI: 10.1038/s41586-025-09073-0

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