Visualizing RNA conformational and architectural heterogeneity in solution

Jienyu Ding, Yun Tzai Lee, Yuba Bhandari, Charles D. Schwieters, Lixin Fan, Ping Yu, Sergey G. Tarosov, Jason R. Stagno, Buyong Ma, Ruth Nussinov, Alan Rein, Jinwei Zhang, Yun Xing Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


RNA flexibility is reflected in its heterogeneous conformation. Through direct visualization using atomic force microscopy (AFM) and the adenosylcobalamin riboswitch aptamer domain as an example, we show that a single RNA sequence folds into conformationally and architecturally heterogeneous structures under near-physiological solution conditions. Recapitulated 3D topological structures from AFM molecular surfaces reveal that all conformers share the same secondary structural elements. Only a population-weighted cohort, not any single conformer, including the crystal structure, can account for the ensemble behaviors observed by small-angle X-ray scattering (SAXS). All conformers except one are functionally active in terms of ligand binding. Our findings provide direct visual evidence that the sequence-structure relationship of RNA under physiologically relevant solution conditions is more complex than the one-to-one relationship for well-structured proteins. The direct visualization of conformational and architectural ensembles at the single-molecule level in solution may suggest new approaches to RNA structural analyses.

Original languageEnglish
Article number714
JournalNature Communications
Issue number1
StatePublished - Dec 2023
Externally publishedYes


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