Three abundant bacterial non‑coding RNAs assemble into protein‑free multistrand complexes, SLAC/Stanford team reports (Kretsch et al., Nature, 6 May 2025).
Cryogenic electron microscopy at resolutions of 2.9 to 3.1 Å has revealed that three bacterial non-coding RNAs can fold into large, symmetric multistrand assemblies without any protein assistance, researchers report in an article preview in Nature.
Using cryogenic electron microscopy at resolutions of 2.9 Å (OLE), 3.1 Å (ROOL), and 3.0 Å (GOLLD), the researchers observed three bacterial RNAs self‑assemble into distinct shapes: OLE, known to interact with proteins in vivo, formed a two‑strand “pipe” dimer without them; ROOL created an eight‑strand hollow nanocage; and GOLLD assembled an even larger 14‑strand shell whose inner cavity rivals a bacterial ribosome’s diameter. Because these architectures are stabilized purely by RNA‑RNA interactions, without any proteins directly involved in their multimerization, they expand what scientists know about how RNA can fold and may provide blueprints for designing RNA‑based sensors or drug‑delivery particles.
These RNAs form stable homo-oligomeric complexes (multiple copies of the same RNA molecule assembling together) without the involvement of any proteins. The researchers describe this as “without precedent among previously characterized natural RNA molecules.”
“We discovered that these RNAs fold into beautiful symmetric complexes without any proteins or other molecules to support them. This is something we haven’t seen before in nature,” said Stanford graduate student and lead author Rachael Kretsch in a SLAC announcement.
From left: Wah Chiu, Rachael Kretsch, and Rhiju Das. The laptop displays a 3D model of a large RNA-only complex, one of three unusual structures the team uncovered using cryo-EM at SLAC. (Alexandre Cassago/SLAC National Accelerator Laboratory)
Who are these RNAs and where do they come from?
The RNAs, nicknamed OLE, ROOL, and GOLLD, vary in size. OLE (Ornate Large Extremophilic RNA), initially found in extremophilic bacteria like heat- and solvent-tolerant Bacillus strains, is 577 nucleotides (nt) long in the version studied. ROOL (Rumen-Originating Ornate Large), discovered in the cow-rumen microbiome, is 659 nt. GOLLD (Giant Ornate Lake- & Lactobacillales-Derived), sourced from a marine metagenomic sample, is the largest at 833 nt. All are several times larger than a typical transfer RNA.
Cryo‑EM shows the ROOL nanocage is about 280 Å across, a little wider than an E. coli ribosome, while GOLLD spans roughly 380 Å, making it one of the largest natural RNA‑only objects ever resolved.
Why might bacteria build such elaborate shells?
Modeling suggests the cages can hinge open to load cargo. One illustration in the paper shows the ROOL shell comfortably enveloping an entire large ribosomal subunit; another shows GOLLD exposing phage‑encoded tRNAs. The authors speculate the RNAs could act as stress‑response containers, delivery pods, or viral‑life‑cycle accessories.
The team’s immediate goals are to pull down binding partners from bacterial extracts and watch whether the cages open or close under different conditions. A control RNA (raiA motif) imaged in the same study remained monomeric, underscoring that not all large RNAs multimerize.
The research could pave the way for the design of similar structures for biomedical or biotechnological purposes, according to the scientists
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