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paywallMB to NatureEnglish · 22 hours ago

Cryo-EM structure of a natural RNA nanocage

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Cryo-EM structure of a natural RNA nanocage

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paywallMB to NatureEnglish · 22 hours ago
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Cryo-EM structure of a natural RNA nanocage - Nature
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Long (>200 nucleotides) non-coding RNAs (lncRNAs) play important roles in diverse aspects of life. Over 20 classes of lncRNAs have been identified in bacteria and bacteriophages through comparative genomics analyses, but their biological functions remain largely unexplored1-3. Due to the large sizes, the structural determinants of most lncRNAs also remain uncharacterized. Here we report the structures of two natural RNA nanocages formed by the lncRNA ROOL (rumen-originating, ornate, large) found in bacterial and phage genomes. ~2.9 Å cryo-electron microscopy (cryo-EM) structures reveal that ROOL RNAs form an octameric nanocage with a 28-nm diameter and 20-nm axial length, whose hollow inside features poorly ordered regions. The octamer is stabilized by numerous tertiary and quaternary interactions, including triple-strand A-minors that we propose to name “A-minor staples”. The structure of an isolated ROOL monomer at ~3.2-Å resolution indicates that nanocage assembly involves a strand-swapping mechanism resulting in quaternary kissing loops. Finally, we show that ROOL RNA fused to an RNA aptamer, tRNA, or microRNA retains its structure forming a nanocage with radially displayed cargos. Our findings therefore may enable the engineering of novel RNA nanocages as delivery vehicles for research and therapeutic applications.

Nature, Published online: 16 June 2025; doi:10.1038/s41586-025-09262-x

Cryo-EM structure of a natural RNA nanocage


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Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

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