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bioRxiv · 10.64898/2026.07.01.735769

Structural assemblies for an RNA world

Ren, Y.·Zhang, Z.·Chen, K.·Li, M.·Xie, Y.·Bai, T.·Huang, B.·Xiao, B.·Westhof, E.·Lilley, D. M. J.·Wang, J.·Miao, Z.·Wei, X.·Huang, L.
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Abstract

Protein homo-oligomerization widely generates symmetric assemblies for encapsulation and scaffolding. Conversely, natural RNA quaternary structures appear limited, with known RNA-only multimers predominantly forming dimers or dihedral assemblies from long transcripts. Whether short RNAs can access broader higher-order assembly space has remained unclear. Here, using cryo-EM, we show that RNAs under 200 nucleotides form three distinct structural classes: a 60-subunit viral-capsid-like icosahedron, non-caged oligomers including a trimer and a strand-exchanged dimer, and a continuous filament assembled from a 57-nucleotide RNA. These structures demonstrate that assembly complexity does not simply scale with RNA length; compact RNAs can specify architectures traditionally associated with proteins. Our findings broaden the known RNA quaternary repertoire, strengthen the structural plausibility of higher-order organization in an RNA world, and establish foundational reference architectures to guide future RNA-based self-assembling nanoparticle design. HighlightsO_LIShort RNAs reveal protein-like assembly principles for an RNA world C_LIO_LIThe first natural RNA-only T=1 icosahedral cage is a viral-capsid-like 60-mer C_LIO_LICompact RNA-RNA interfaces encode global curvature, valency and propagation C_LIO_LIRNA motifs assemble into closed cages, finite oligomers and extended filaments C_LI

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Ren, Y., Zhang, Z., Chen, K., Li, M., Xie, Y., Bai, T., Huang, B., Xiao, B., Westhof, E., Lilley, D. M. J., Wang, J., Miao, Z., Wei, X., Huang, L.. 2026-07-01. Structural assemblies for an RNA world. https://doi.org/10.64898/2026.07.01.735769

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