Publication Date

12-19-2025

Document Type

Article

Organizational Units

College of Natural Science and Mathematics, Chemistry and Biochemistry

Keywords

RNA nanostructures, Self assembly, Atomic force microscopy, Light scattering

Abstract

Recent developments in RNA nanotechnology have led to an increase in the design of specific, higher-order RNA structures, which will ultimately be used in drug delivery and immunomodulation applications. As researchers create RNA nanostructures with the intention of making them a standard tool in molecular biologists' toolkits, further investigation is required into the robustness of RNA designs. Primarily, in what different molecular contexts are the designed and intended nanostructures stable? In this work, we show that RNA nanostructure self-assembly is highly sensitive to environmental conditions by using second-order right-angle light scattering. While a test RNA hexagonal grid nanostructure forms correctly through 120° kissing loops under ideal conditions, small variations in salt conditions and annealing times cause the nanostructure to form less structured variants. Tertiary contacts for self-assembly require magnesium and break over a broad range of low temperatures, melting at 43 °C. In contrast, this was found to be considerably lower than the secondary structure melting, which occurred at 75 °C. This work highlights the importance of quantitatively and thermodynamically characterizing self-assembling nanostructures as they are increasingly deployed for engineering and therapeutic applications.

Copyright Date

1-6-2026

Copyright Statement / License for Reuse

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

Rights Holder

Jordan Aposhian, Surya Pratap S. Deopa, Scott Horowitz, and Joseph D. Yesselman

Provenance

Received from Elsevier

File Format

application/pdf

Language

English (eng)

Extent

13 pgs

File Size

4.00 MB

Publication Statement

Copyright is held by the Authors. User is responsible for all copyright compliance. This article was originally published as

Aposhian, J., Deopa, S. P. S., Horowitz, S., & Yesselman, J. D. (2026). Self-Assembling RNA Nanostructures are Highly Sensitive to Environmental Conditions. Journal of Molecular Biology, 438(5). https://doi.org/10.1016/j.jmb.2025.169601

Supplementary File Description

"Graphical Abstract", JPG File, 1 Image, 133 KB

Publication Title

Journal of Molecular Biology

Volume

438

Issue

5

First Page

169601

ISSN

0022-2836

PubMed ID

41422840



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