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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.

2026-07-01 evolutionary biology
10.64898/2026.07.01.735769 bioRxiv
Show 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.

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